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US20030176325A1 - Modified peptide nucleic acid (PNA) molecules - Google Patents

Modified peptide nucleic acid (PNA) molecules Download PDF

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US20030176325A1
US20030176325A1 US10/083,259 US8325901A US2003176325A1 US 20030176325 A1 US20030176325 A1 US 20030176325A1 US 8325901 A US8325901 A US 8325901A US 2003176325 A1 US2003176325 A1 US 2003176325A1
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Peter Nielsen
Liam Good
Henrik Hansen
Frederik Beck
Leila Malik
Carsten Schou
Margit Wissenbach
Birgit Giwercman
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Pantheco AS
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Priority to US10/083,259 priority Critical patent/US20030176325A1/en
Assigned to NIELSEN, PETER E. reassignment NIELSEN, PETER E. CROSS-REFERENCE OF ASSIGNMENT FILED IN UNITED STATES APPLICATION NO. 09689155, RECORDED ON MARCH 9, 2001 AT REEL 011611 AND FRAME 0103. Assignors: GOOD, LIAM
Assigned to PANTHECO A/S reassignment PANTHECO A/S ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HANSEN, HENRIK FRYDENLUND, MALIK, LEILA, SCHOU, CARSTEN, BECK, FREDERIK, GIWERCMAN, BIRGIT KJAELDGAARD, WISSENBACH, MARGIT
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/15—Nucleic acids forming more than 2 strands, e.g. TFOs
    • C12N2310/152—Nucleic acids forming more than 2 strands, e.g. TFOs on a single-stranded target, e.g. fold-back TFOs
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • C12N2310/3181—Peptide nucleic acid, PNA
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
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    • C12N2310/3233—Morpholino-type ring
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3513—Protein; Peptide

Definitions

  • the present invention relates to novel drugs for use in combating, for example, infectious microorganisms, particularly bacteria. More specifically, the invention relates to peptide nucleic acid (PNA) sequences that are modified in order to obtain novel PNA molecules which exhibit enhanced anti-infective properties.
  • PNA peptide nucleic acid
  • antibiotics are products of natural microbic populations and resistant traits found in these populations can disseminate between species and appear to have been acquired by pathogens under selective pressure from antibiotics used in agriculture and medicine (Davis et al., Science, 1994, 264, 375).
  • Antibiotic resistance may develop in bacteria harbouring genes that encode enzymes that either chemically alter or degrade antibiotics.
  • Resistant bacteria may also encode enzymes that make the cell wall impervious to antibiotics or encode efflux pumps that eject antibiotics from the cell before the antibiotics can exert their effects. Due to the emergence of antibiotic-resistant bacterial pathogens, a need for new therapeutic strategies has arisen.
  • One strategy for avoiding problems caused by resistance genes is the development of anti-infective drugs from novel chemical classes for which specific resistance traits do not exist.
  • Antisense agents offer a novel strategy for combatting disease, as well as opportunities to employ new chemical classes in drug design.
  • Oligonucleotides can interact with native DNA and RNA in several ways, including duplex formation between an oligonucleotide and a single-stranded nucleic acid and triplex formation between an oligonucleotide and double-stranded DNA to form a triplex structure.
  • the use of anti-sense methods in basic research has been encouraging, and antisense oligonucleotide drug formulations that target viral and disease-causing human genes are progressing through clinical trials.
  • Antisense inhibition of bacterial genes could also have wide application; however, few attempts have been made to extend antisense technology to bacteria.
  • PNA Peptide nucleic acids
  • PNA Peptide nucleic acids
  • the deoxyribose backbone of DNA is replaced in PNA by a pseudo-peptide backbone (Nielsen et al., Science, 1991, 254, 1475; see FIG. 1).
  • Each subunit, or monomer has a naturally occurring or non-naturally occurring nucleobase attached to the backbone.
  • One such backbone consists of repeating units of N-(2-aminoethyl)glycine linked through amide bonds.
  • PNA hybridizes to complementary nucleic acids through Watson and Crick base pairing and helix formation results (Egholm et al., Nature, 1993, 365, 566).
  • the Pseudo-peptide backbone provides superior hybridization properties (Egholm et al., Nature, 1993, 365, 566), resistance to enzymatic degradation (Demidov et al., P.E. Biochem. Pharmacol., 1994, 48, 1310) and access to a variety of chemical modifications (Nielsen et al., Chemical Society Reviews, 1997, 73).
  • PNA binds both DNA and RNA to form PNA/DNA or PNA/RNA duplexes.
  • the resulting PNA/DNA or PNA/RNA duplexes are bound with greater affinity than corresponding DNA/DNA or DNA/RNA duplexes, as determined by T m s.
  • the thermal stability of PNA/DNA and PNA/RNA duplexes could be due to the lack of charge repulsion in the neutral backbone of PNA.
  • PNA has also been shown to hybridize to DNA with increased specificity, as compared to DNA/DNA duplexes. When a PNA/DNA duplex mismatch is melted relative to a DNA/DNA duplex, an 8 to 20° C. drop in the T m results.
  • PNA oligomers form extremely stable PNA 2 -DNA triplexes with sequence-complementary targets in DNA or RNA oligomers.
  • PNAs may bind to double-stranded DNA or RNA by helix invasion.
  • PNA nuclease and protease reisitance of the PNA polyamide backbone.
  • PNA is not recognized by either nucleases or proteases and is thus not susceptible to cleavage; consequently, PNAs are resistant to degradation by enzymes, unlike nucleic acids and peptides.
  • target-bound PNA can cause steric hindrance of DNA and RNA polymerases, reverse transcripase, telomerase and ribosomes (Hanvey et al., Science, 1992, 258, 1481; Knudsen et al., Nucleic Acids Res., 1996, 24, 494; Good et al., Proc. Natl. Acad. Sci USA, 1998, 95, 2073; Good, et al., Nature Biotechnology, 1998, 16, 355).
  • a general difficulty in the use of antisense agents is cell uptake.
  • a variety of strategies to improve uptake have been explored and reports of improved uptake into eukaryotic cells using lipids (Lewis et al., Proc. Natl. Acad. Sci. USA, 1996, 93, 3176), encapsulation (Meyer et al., J. Biol. Chem., 1998, 273, 15621) and carrier strategies (Nyce et al., Nature, 1997, 385, 721; Pooga et al., Nature Biotechnology, 1998, 16, 857) have been made.
  • WO 99/05302 discloses a PNA conjugate consisting of PNA and the transporter peptide transportan, in which the peptide can be used for transport cross a lipid membrane and for delivery of the PNA into interactive contact with intracellular polynucleotides.
  • U.S. Pat. No. 5,777,078 discloses a pore-forming compound which comprises a delivery agent that recognizes the target cell and is linked to a pore-forming agent, such as a bacterial exotoxin. The compound is administered together with a drug such as PNA.
  • PNAs have unique advantages as an antisense agent for microorganisms.
  • PNA-based antisense agents can control cell growth and growth phenotypes when targeted to Escherichia coli rRNA and mRNA (Good et al., Proc. Natl. Acad. Sci USA, 1998, 95, 2073; Good et al., Nature Biotechnology, 1998, 16, 355; and WO 99/13893).
  • U.S. Pat. No. 5,834,430 discloses the use of potentiating agents, such as short cationic peptides, in the potentiation of antibiotics.
  • the agent and the antibiotic are co-administered.
  • WO 96/11205 discloses PNA conjugates, wherein a conjugated moiety may be placed on terminal or non-terminal parts of the backbone of PNA in order to functionalize the PNA.
  • the conjugated moieties may be reporter enzymes or molecules, steroids, carbohydrate, terpenes, peptides, proteins, etc.
  • the conjugates possess improved transfer properties for crossing cellular membranes; however, WO 96/11205 does not disclose conjugates that can cross bacterial membranes.
  • WO 98/52614 discloses a method of enhancing transport over biological membranes, e.g., a bacterial cell wall.
  • biologically active agents such as PNA may be conjugated to a transporter polymer in order to enhance transmembrane transport.
  • the transporter polymer consists of 6-25 subunits, at least 50% of which contain a guanidino or amidino side chain moiety, and wherein at least 6 contiguous subunits contain guanidino and/or amidino side chains.
  • a preferred transporter polymer is a polypeptide containing 9-arginine.
  • the present invention relates to a new strategy for combatting bacteria.
  • Antisense PNA can inhibit the growth of bacteria; however, due to slow diffusion of PNA across the bacterial cell wall, the use of PNA as an antibiotic has not been possible.
  • a practical application for PNA in combatting bacteria can be achieved by modifying the PNA through linkage of a peptide or peptide-like sequence that enhances the activity of the PNA.
  • one aspect of the present invention is directed to a modified PNA molecule, and pharmaceutically acceptable salt thereof, of Formula I:
  • L is a linker or a bond
  • Peptide is any amino acid sequence
  • PNA is a Peptide Nucleic Acid.
  • the present invention is directed to a modified PNA molecule of Formula I
  • Peptide is a cationic peptide or cationic peptide analogue or a functionally similar moiety, the peptide or peptide analogue having the Formula II:
  • A is from 1 to 8 non-charged amino acids and/or amino acid analogs
  • B is from 1 to 3 positively charged amino acids and/or amino acid analogs
  • C is from 0 to 4 non-charged amino acids and/or amino acid analogs
  • D is from 0 to 3 positively charged amino acids and/or amino acid analogs
  • n is 1-10, and the total number of amino acids and/or amino acid analogs is from 3 to 20.
  • the Peptide of the present invention comprises from 2 to 60 amino acids.
  • the amino acids can be negatively charged, non-charged, or positively charged naturally-occurring, rearranged, or modified amino acids.
  • the peptide comprises from 2 to 18 amino acids, and most preferably from 5 to 15 amino acids.
  • a in Formula II comprises from 1 to 6 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs.
  • A comprises from 1 to 4 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs.
  • the modified PNA molecules of Formula I are used, for example, in the treatment or prevention of infections caused by Escherichia coli or vancomycin-resistant enterococci such as Enterococcus faecalis and Enterococcus faecium or infections caused by methicillin-resistant and methicillin-vancomycin-resistant Staphylococcus aureus.
  • the peptide moiety in a modified PNA molecule is linked to the PNA sequence via the amino (N-terminal) or carboxy (C-terminal) end.
  • the peptide is linked to the PNA sequence via the carboxy end.
  • modified PNA molecules are used in the manufacture of medicaments for the treatment or prevention of infectious diseases or for disinfecting non-living objects.
  • the invention concerns a composition for treating or preventing infectious diseases or disinfecting non-living objects.
  • the invention concerns the treatment or prevention of infectious diseases or treatment of non-living objects.
  • the present invention is directed to a method of identifying specific advantageous antisense PNA sequences that may be used in the modified PNA molecule according to the invention.
  • the present invention relates to other antisense oligonucleotides with the ability to bind to both DNA and RNA.
  • Oligonucleotide analogs are oligomers having a sequence of nucleotide bases (nucleobases) and a subunit-to-subunit backbone that allows the oligomer to hybridize to a target sequence in an mRNA by Watson-Crick base pairing, to form an RNA/Oligomer duplex in the target sequence.
  • the oligonucleotide analog may have exact sequence complementarity to the target sequence or near complementarity, as long as the hybridized duplex structure formed has sufficient stability to block or inhibit translation of the mRNA containing target sequence.
  • Oligonucleotide analogs of the present invention are selected from the group consisting of Locked Nucleoside Analogues (LNA) as described in International PCT Publication WO99/14226, oligonucleotides as described in International PCT Publication WO98/03533 or antisense oligomers, in particular morpholino analogs as described in International PCT Publication WO98/32467.
  • LNA Locked Nucleoside Analogues
  • L is a linker or a bond
  • Peptide is any amino acid sequence
  • Oligon is an oligonucleotide or analog thereof.
  • FIG. 1 shows representative chemical structures of DNA and PNA oligomers.
  • FIG. 2 is a schematic showing a representative conjugation using SMCC.
  • FIGS. 3A and 3B show the nucleotide sequence of the mrcA (ponA) gene encoding PBP1A.
  • the sequence of the gene (accession number X02164) was obtained from the EMBL sequence database (Heidelberg, Germany) (Broome-Smith et al., Eur J Biochem, 1985, 147, 437). Two possible start codons have been identified (bolded). Bases 1-2688 are shown (ending with stop codon).
  • FIGS. 4A and 4B show the nucleotide sequence of the mrdA gene encoding PBP2.
  • the sequence (accession number AE000168, bases 4051-5952, numbered 1-2000) was obtained from the E. coli genome database at the NCBI (Genbank, National Center for Biotechnology Information, USA). The start codon is bolded.
  • FIG. 5 shows representative chemical structures of different succinimidyl based linking groups used in conjugation of a Peptide and PNA
  • the present invention relates, in part, to a modified oligonucleotide of Formula III:
  • L is a linker or a bond
  • Peptide is any amino acid sequence
  • Oligon is an oligonucleotide or analog thereof.
  • Oligons useful for the invention include, but are not limited to, oligonucleotide analogs such as, for example, Locked Nucleoside Analogues (LNA), as described in International PCT Publication WO99/14226, or analogs as described in International PCT Publication WO98/03533, or morpholino analogs as described in International PCT Publication WO98/32467, each of which are incorporated herein by reference in their entirety.
  • LNA Locked Nucleoside Analogues
  • Antisense PNAs can inhibit bacterial gene expression with gene and sequence specificity (Good et al., Proc. Natl. Acad. Sci USA, 1998, 95, 2073; Good et al., Nature Biotechnology, 1998, 16, 355; and WO 99/13893). Antisense PNAs may prove to be a practical tool for functional genomics and a source of novel antimicrobial drugs. However, improvements in standard PNA techniques are required in order to increase antisense potencies. The major limit to antisense activity appears to be cellular entry. Bacteria effectively exclude the entry of large molecular weight foreign compounds, and previous results of in vitro and cellular assays seem to demonstrate that the cell barrier restricts antisense effects. Accordingly, the present invention concerns strategies to improve the activity of antisense PNAs.
  • short cationic peptides lead to improved PNA uptake over the bacterial cell wall. It is believed that the short peptides act by penetrating the cell wall and allowing the modified PNA molecule to cross the cell wall and gain access to structures inside the cell, such as the genome, mRNAs, the ribosome, etc. Improved accessibility to the nucleic acid target or improved binding of the PNA may also add to the overall effect observed.
  • nanomolar concentrations of PNA molecules modified with short, activity-enhancing peptides enable specific and efficient inhibition of bacterial gene expression.
  • Antisense potencies in this concentration range are consistent with practical applications of the technology. It is believed that the present invention demonstrates for the first time that peptides with a certain pattern of cationic and lipophilic amino acids can be used as carriers to deliver agents and other compounds into micro-organisms, such as bacteria. Further, the present invention has made it possible to administer PNA in an efficient concentration that is also acceptable to the patient. Accordingly, the present invention concerns novel modified PNA molecules of the formula:
  • L is a linker or a bond
  • PNA is a peptide nucleic acid sequence
  • Peptide is a cationic peptide or peptide analog or a functionally similar moiety, the peptide or peptide analog preferably having the formula:
  • A comprises from 1 to 8 non-charged amino acids and/or amino acid analogs
  • B comprises from 1 to 3 positively charged amino acids and/or amino acid analogs
  • C comprises from 0 to 4 non-charged amino acids and/or amino acid analogs
  • D comprises from 0 to 3 positively charged amino acids and/or amino acid analogs
  • n is 1-10
  • the total number of amino acids and/or amino acid analogs is from 3 to 20.
  • a preferred group of modified PNA molecules is the group wherein A comprises from 1 to 6 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs. In another preferred group, A comprises from 1 to 4 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs.
  • cationic amino acids and amino acid analogs and “positively charged amino acids and amino acid analogs” include, but are not limited to, any natural or non-naturally occurring amino acids or amino acid analogs that have a positive charge at physiological pH.
  • non-charged amino acids or amino acid analogs includes any natural or non-naturally occurring amino acids or amino acid analogs that have no charge at physiological pH.
  • Positively charged amino acids and amino acid analogs include lysine (Lys, K), arginine (Arg, R), diamino butyric acid (DAB), and ornithine (Orn). The skilled artisan is aware of further positively charged amino acids and amino acid analogs.
  • cationic peptide includes any natural or non-naturally occurring peptide that has a positive charge at physiological pH.
  • peptide analog includes any natural or non-naturally occurring peptide, or derivative thereof.
  • the non-charged amino acids and amino acid analogs include, but are not limited to, the naturally occurring amino acids alanine (Ala, A), valine (Val, V), leucine (Leu, L), isoleucine (Ile, I), proline (Pro, P), phenylanaline (Phe, F), tryptophan (Trp, W), methionine (Met, M), glycine (Gly, G), serine (Ser, S), threonine (Thr, T), cysteine (Cys, C), tyrosine (Tyr, Y), asparagine (Asn, N) and glutamine (Gln, Q), and the non-naturally occurring amino acids 2-aminobutyric acid, ⁇ -cyclohexylalanine, 4-chlorophenylalanine, norleucine and phenylglycine.
  • non-charged amino acids and amino acid analogs are selected from the naturally occurring non-polar amino acids Ala, Val, Leu, Ile, Phe, Trp and Met or the non-naturally occurring non-polar amino acids ⁇ -cyclohexylalanine, 4-chlorophenylalanine and norleucine.
  • the term “functionally similar moiety” includes all peptide-like molecules that functionally mimic the Peptide as defined above and thus impart to the PNA molecule the same advantageous properties as the peptides comprising natural and non-natural amino acids as defined above.
  • Examples of preferred modified PNA molecules according to the invention include, but are not limited to, (Lys Phe Phe) 3 Lys-L-PNA and any subunits thereof comprising at least three amino acids.
  • One preferred Peptide is (Lys Phe Phe) 3 (SEQ ID NO: 1).
  • Others include (Lys Phe Phe) 2 Lys Phe (SEQ ID NO:2), (Lys Phe Phe) 2 Lys (SEQ ID NO:157), (Lys Phe Phe) 2 (SEQ ID NO:3), Lys Phe Phe Lys Phe (SEQ ID NO:4), Lys Phe Phe Lys (SEQ ID NO:5) and Lys Phe Phe.
  • FFRFFRFFR SEQ ID NO:6
  • LLKLLKLLK SEQ ID NO:7
  • LLRLLRLLR SEQ ID NO:8
  • LLKKLAKAL SEQ ID NO:9
  • KRRWPWWPWKK SEQ ID NO:10
  • KFKVKFVVKK SEQ ID NO:11
  • LLKLLLKLLLK SEQ ID NO:12
  • LLKKLAKALK SEQ ID NO:13
  • derivatives of the peptides having conservative amino acid substitutions, or insertions or deletions.
  • a third group of preferred Peptides is RRLFPWWWPFRRVC (SEQ ID NO:14), GRRWPWWPWKWPLIC (SEQ ID NO:15), LVKKVATTLKKIFSKWKC (SEQ ID NO:16), KKFKVKFVVKKC (SEQ ID NO:17) and any subunit thereof comprising at least 3 amino acids whereof at least one amino acid is a positively charged amino acid.
  • a fourth group of preferred Peptides is magainis (Zasloff, Proc. Natl. Acad. Sci.
  • the number of amino acids in the peptide can be from 3 to 20. Preferably, at least 3 amino acids, at least one of which is a positively charged amino acid, are necessary to obtain the advantageous effect. On the other hand, the upper limit for the number of amino acids in the peptide seems only to be set by the overall size of the PNA molecule. Preferably, the total number of amino acids is 15 or less, more preferably 12 or less, and most preferably 10 or less.
  • the PNA contains from 5 to 20 nucleobases, preferably from 7-15 nucleobases, and most preferably from 8 to 12 nucleobases.
  • the PNA backbone is aminoethylglycine as shown in FIG. 1. PNAs are described in, for example, WO 92/20702 and WO 92/20703, each of which is incorporated herein by reference in its entirety.
  • the PNA molecule is connected to the Peptide moiety through direct binding or through a linker.
  • a variety of linking groups can be used to connect the PNA with the Peptide. Linking groups are described in, for example, WO 96/11205 and WO98/52614, each of which is incorporated herein by reference in its entirety. Some linking groups may be advantageous in connection with specific combinations of PNA and Peptide.
  • Preferred linking groups include 8-amino-3,6-dioxaoctanoic acid (ADO), succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), 6-aminohexanoic acid (AHEX or AHA), 4-aminobutyric acid, 4-aminocyclohexylcarboxylic acid, succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxy-(6-amido-caproate) (LCSMCC), succinimidyl m-maleimido-benzoylate (MBS), succinimidyl N- ⁇ -maleimido-caproylate (EMCS), succinimidyl 6-( ⁇ -maleimido-propionamido) hexanoate (SMPH), succinimidyl N-( ⁇ -maleimido acetate) (AMAS), succinimidyl 4-(p-maleimido
  • the linking group is a combination of the ⁇ .ALA linking group or the ADO linking group with any of the other above mentioned linking groups.
  • preferred linkers include, but are not limited to, -achc- ⁇ .ala-, -achc-ado-, -lcsmcc- ⁇ .ala-, -mbs- ⁇ .ala-, -emcs- ⁇ .ala-, -lcsmcc-ado-, -mbs-ado-, -emcs-ado- or -smph-ado-.
  • linkers include the following: -achc- ⁇ .ala-, -lcsmcc-ado- and -mbs-ado-.
  • succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) is used in the process of linking PNA to the peptide, it is necessary to add a cysteine (C) or a similar thiol containing moiety to the terminal end of the peptide (see FIG. 2).
  • cysteine C
  • amino acids such as glycine
  • the Peptide is normally linked to the PNA sequence via the amino or carboxy end.
  • the PNA sequence may also be linked to an internal part of the peptide, or the PNA sequence is linked to a peptide via both the amino and the carboxy end.
  • modified PNA targets is not limited to targets of modified PNA molecules and is equally applicable to targets of the modified oligonucleotides of the invention.
  • the modified PNA molecules of the present invention comprise PNA oligomer sequences that are complementary to at least one target nucleotide sequence in a microorganism, such as a bacterium.
  • the target may be a nucleotide sequence of any RNA that is essential for the growth, and/or reproduction of the bacteria.
  • the target may be a gene encoding a factor responsible for resistance to antibiotics.
  • the functioning of the target nucleotide sequence is essential for the survival of the bacteria and the functioning of the target nucleic acid is blocked by the PNA sequence, in an antisense manner.
  • the binding of a PNA strand to a DNA or RNA strand can occur in one of two orientations, anti-parallel or parallel.
  • the term “complementary” as applied to PNA does not in itself specify the orientation parallel or anti-parallel. It is significant that the most stable orientation of PNA/DNA and PNA/RNA is anti-parallel.
  • PNA targeted to single-stranded RNA is complementary in an anti-parallel orientation.
  • a bis-PNA consisting of two PNA oligomers covalently linked to each other is targeted to a homopurine sequence (consisting of only adenine and/or guanine nucleotides) in RNA (or DNA), with which it can form a PNA 2 -RNA (PNA 2 -DNA) triple helix.
  • Target genes can be chosen based upon knowledge about bacterial physiology.
  • a target gene can be found among those involved in one of the major process complexes: cell division, cell wall synthesis, protein synthesis (translation), nucleic acid synthesis, fatty acid metabolism, and gene regulation.
  • a target gene can also be involved in antibiotic resistance.
  • a further consideration in selecting target genes is that some physiological processes are primarily active in dividing cells whereas others are active under non-dividing circumstances as well.
  • PBPs penicillin binding proteins
  • the targets of, e.g., the beta-lactam antibiotic penicillin which are involved in the final stages of cross-linking of the murein sacculus.
  • E. coli has 12 PBPs, which include the high molecular weight PBPs: PBP1a, PBP1b, PBP1c, PBP2 and PBP3, and seven low molecular weight PBPs: PBP 4-7, DacD, AmpC and AmpH.
  • PBP 4-7 the high molecular weight PBPs are known to be essential for growth and have therefore been chosen as targets for PNA antisense molecules.
  • Protein biosynthesis is an important process throughout the bacterial cell cycle; consequently, targeting enzymes involved in protein biosynthesis is not dependent upon cell division.
  • Proteins involved in DNA and RNA synthesis are also antibiotic targets.
  • a target protein in DNA synthesis is gyrase, which acts in replication, transcription, repair and restriction.
  • the enzyme consists of two subunits, both of which are candidate targets for PNA.
  • Examples of potential targets primarily activated in dividing cells are rpoD, gyrA, gyrB, (transcription), mrcA (ponA), mrcB (ponb, pbpF), mrdA, ftsI (pbpB) (cell wall biosynthesis), ftsQ, ftsA and ftsZ (cell division).
  • Examples of potential targets also activated in non-dividing cells are infA, infB, infC, tufA/tufB, tsf, fusA, prfA, prfB, and prfC, (translation).
  • antibiotic resistance-genes examples include, but are not limited to, genes encoding beta-lactamases and genes encoding chloramphenicol acetyl transferase. PNAs against such resistance genes could be used against resistant bacteria.
  • a further potential target gene is the acpP gene encoding the acyl carrier protein of E. Coli .
  • ACP acyl carrier protein
  • ACP is a small and highly soluble protein, which plays a central role in type I fatty acid synthase systems. Intermediates of long chain fatty acids are covalently bound to ACP by a thioester bond between the carboxyl group of the fatty acid and the thiol group of the phosphopanthetheine prosthetic group.
  • ACP is one of the most abundant proteins in E. coli , constituting 0.25% of the total soluble protein (ca 6 ⁇ 10 4 molecules per cell). The cellular concentration of ACP is regulated, and overproduction of ACP from an inducible plasmid is lethal to E. coli cells.
  • Infectious diseases are caused by micro-organisms including bacteria, viruses, protozoa, worms and arthropods.
  • PNA can be modified and used to target RNA in such micro-organisms, whether the micro-organisms are sensitive or resistant to antibiotics.
  • microorganisms that can be treated in accordance with the present invention include, but are not limited to, Gram-positive bacteria such as Streptococcus, Staphylococcus, Peptococcus, Bacillus, Listeria, Clostridium, Propionebacteria; Gram-negative bacteria such as Bacteroides, Fusobacterium, Escherichia, Klebsiella, Salmonella, Shigella, Proteus, Pseudomonas, Vibrio, Legionella, Haemophilus, Bordetella, Brucella, Campylobacter, Neisseria, Branhamella; and organisms that stain poorly or not at all with Gram's stain such as Mycobacteria, Treponema, Leptospira, Borrelia, Mycoplasma, Clamydia, Rickettsia and Coxiella,
  • bacteria include methicillin-resistant and methicillin-vancomycin-resistant Staphylococcus aureus , vancomycin-resistant enterococci such as Enterococcus faecalis and Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae and cephalosporin and quinolone resistant gram negative rods (coliforms) such as E. coli, Klebsiella pneumoniae, Pseudomonas species and Enterobacter species. Recently, pan antibiotic (including carbapenems) resistant gram negative bacilli have emerged.
  • Methicillin-resistant S. aureus (Chambers, Clin Microbiol Rev, 10, 781; Elliott, Current Medical Literature-Surgical Infections, 1997, 9), methicillin-vancomycin resistant S. aureus (VMRSA), and vancomycin resistant enterococci (VRE) have emerged as major nosocomial pathogens (House of Lords Select Committee on Science and Technology. Resistance to antibiotics and other antimicrobial agents. London: HMSO, 1998; Arthur et al., Trends Microbiol, 1996, 4, 410; Zervos, New, 1996, 4, 385; Carmelli et al., Arch Intern Med, 1999, 159, 2461).
  • Vancomycin is currently the most reliable treatment for infections caused by MRSA, but the potential transfer of resistance genes from VRE to MRSA may leave few therapeutic options in the future. VRE provide a reservoir of vancomycin resistance genes and can also cause infections in patients with compromised immunity. Some VRE strains exhibit resistance to all major classes of antibiotic and in some hospitals in the United States VRE are responsible for more than 20% of enterococcal infections (Mcneeley et al., Pediatr Infect Dis J, 1998,17, 184; Carmelli et al., Arch Intern Med, 1999,159, 2461).
  • S. aureus exhibiting intermediate vancomycin resistance (VISA), as well as VMRSA, have now been reported in several centers/hospitals worldwide (Johnson, J Antimicrob Chemother, 1998, 42, 289; Hiramatsu et al., Lancet, 1997, 350, 1670). Of the S. aureus isolates from the U.S.A., Europe, and Japan, 60-72% were MRSA. Multi-drug-resistant MRSA are the most common cause of surgical site infections, comprising 61% of all S.
  • Coagulase negative staphylococci such as S. epidermidis
  • CNS Coagulase negative staphylococci
  • S. epidermidis are an important cause of infections associated with prosthetic devices and catheters (Vincent et al., LAMA, 1995, 27, 639).
  • CNS display lower virulence than S aureus, they have intrinsic low-level resistance to many antibiotics, including beta-lactams and glycopeptides.
  • many of these bacteria produce slime (biofilm), making the treatment of prosthetic associated infections difficult and often necessitating the removal of the infected prosthesis or catheter (Costerton et al., Ann Rev Microbiol., 1987, 41, 435).
  • Streptococcus pneumoniae regarded as fully sensitive to penicillin for many years, has now acquired the genes for resistance to oral streptococci. The prevalence of these resistant strains is increasing rapidly worldwide, which will limit the therapeutic options in serious pneumococcal infections, including meningitis and pneumonia (Baquero, Microb Drug Resist, 1995, 1, 115). Streptococcus pneumoniae is the leading cause of infectious morbidity and mortality worldwide. In the U.S.A. pneumococcus is responsible for an estimated 50,000 cases of bacteremia, 3,000 cases of meningitis, 7 million cases of otitis media, and several hundred thousand cases of pneumonia.
  • the overall yearly incidence of pneumococcal bacteremia is estimated to be 15 to 35 cases per 100,000.
  • Current immunization of small children and the elderly have not addressed the high incidence of pneumococcal infection (Dowell, Arch Intern Med, 1999, 159, 2461; Communicable Disease Report (CDN), 1999, 10, 7; Baquero, Microb Drug Resist, 1995, 1, 115).
  • Multi-drug resistant strains were isolated in the late 1970's and are now encountered worldwide (Baquero, Microb Drug Resist, 1995, 1, 115).
  • Pseudomonas aeruginosa Pseudomonads species including Burkholderia cepacia and Xanthomonas malthophilia, Enterobacteriaceae including E. coli , Enterobacter species, and Klebsiella species, account for the majority of isolates in which resistance has emerged (Livermore, Commun Dis Public Health, 1998, 1, 74; Livermore, J Antimicrob Chemother, 1997, 39, 673; House of Lords Select Committee on Science and Technology. Resistance to antibiotics and other antimicrobial agents. London: HMSO, 1998). Cystitis, pneumonia, septicaemi, and postoperative sepsis are the most common types of infections.
  • ICU intensive care unit
  • the low-permeability cell envelope of P. aeruginosa differs from that of E. coli . Forty-six percent of P. aeruginosa isolates from Europe are resistant to one or more antibiotic. The ability of P. aeruginosa to produce slime (biofilm), and its rapid development of resistance during treatment, often leads to therapy failure. Multidrug resistant P. aeruginosa has also become endemic within some specialized ICUs, such as those treating burns patients and cystic fibrosis patients (Hsueh et al., J Clin Microbiol, 1998, 36, 1347; Bert et al., J Antimicrob Chemother, 1996, 37, 809).
  • modified PNA molecules can be used to identify preferred targets for PNAs.
  • modified PNA molecules are used for the identification of PNA sequences that are effective in blocking essential functions in bacteria.
  • Various PNA sequences are incorporated into modified PNA molecules, which are then tested for their ability to inhibit or reduce the growth of bacteria.
  • Another embodiment of the invention involves a method of identifying PNA sequences that are useful in inhibiting or reducing the growth of one or more bacteria.
  • the method involves mixing modified PNA molecules of Formula I, which contain different PNA sequences, with one or more bacteria.
  • the PNA sequences are selected so as to be complementary to at least one nucleotide sequence in each bacteria. PNA sequences that are effective in inhibiting or reducing the growth of one or more bacteria are identified.
  • the compounds of Formula I can be prepared in the form of pharmaceutically acceptable salts, especially acid-addition salts, including salts of organic acids and mineral acids.
  • pharmaceutically acceptable salts refers to derivatives of the modified PNAs of Formula I and the modified oligonucleotides of Formula III wherein the parent molecule is modified by making acid or base salts thereof.
  • pharmaceutically acceptable refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of reasonable medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
  • Examples of pharmaceutically acceptable salts include, but are not limited to, salts of organic acids such as formic acid, fumaric acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, succinic acid, malic acid, tartaric acid, citric acid, benzoic acid, salicylic acid, and the like.
  • Suitable inorganic acid-addition salts include salts of hydrochloric, hydrobromic, sulphuric and phosphoric acids, and the like.
  • Further examples of pharmaceutically acceptable inorganic or organic acid addition salts include the pharmaceutically acceptable salts listed in Journal of Pharmaceutical Science, 1977, 66, 2, which are known to the skilled artisan.
  • Pharmaceutically acceptable acid addition salts also include the hydrates that the compounds of the invention are able to form.
  • the acid addition salts can be obtained as the direct products of compound synthesis.
  • the free base can be dissolved in a suitable solvent containing the appropriate acid, and the salt isolated by evaporating the solvent or otherwise separating the salt and solvent.
  • the compounds of this invention can form solvates with standard low molecular weight solvents using methods known to the skilled artisan.
  • the invention provides a composition for use in inhibiting growth or reproduction of infectious micro-organisms, comprising a modified PNA molecule according to the present invention.
  • composition includes pharmaceutically acceptable compositions.
  • the inhibition of the growth of micro-organisms is obtained through treatment with either the modified PNA molecule alone or in combination with antibiotics or other anti-infective agents.
  • the composition comprises two or more different modified PNA molecules.
  • a second modified PNA molecule can be used to target the same bacteria as the first modified PNA molecule or to target different bacteria. In the latter situation, specific combinations of target bacteria may be selected for treatment.
  • the target can be one or more genes that confer resistance to one or more antibiotics in one or more bacteria. In such a situation, the composition or the treatment further comprises the use of said antibiotic(s).
  • the present invention includes within its scope pharmaceutical compositions comprising, as an active ingredient, at least one of the compounds of the general Formula I, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent.
  • compositions of the present invention can be prepared by conventional techniques, e.g., as described in Remington: The Science and Practice of Pharmacy, 19 th Ed., 1995.
  • the compositions can appear in conventional forms, for example, capsules, tablets, aerosols, solutions, suspensions, or topical applications.
  • compositions include a compound of Formula I or III, or a pharmaceutically acceptable acid addition salt thereof, associated with a pharmaceutically acceptable excipient, which may be a carrier or a diluent.
  • a pharmaceutically acceptable excipient which may be a carrier or a diluent.
  • the composition can be diluted by a carrier, or enclosed within a carrier that can be in the form of a capsule, sachet, paper or other container.
  • conventional techniques for the preparation of pharmaceutical compositions may be used.
  • the active compound can be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of a ampoule, capsule, sachet, paper, or other container.
  • the carrier When the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material which acts as a vehicle, excipient, or medium for the active compound.
  • the active compound can be adsorbed on a granular solid container, for example, in a sachet.
  • suitable carriers include water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatine, lactose, terra alba, sucrose, glucose, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid, or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone.
  • the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax.
  • the formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents, thickeners or flavouring agents.
  • the formulations of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the patient by employing procedures well known in the art.
  • compositions can be sterilized and mixed, if desired, with auxiliary agents, emulsifiers, salt for influencing osmotic pressure, buffers and/or coloring substances, and the like, that do not deleteriously react with the active compounds.
  • the route of administration can be any route that effectively transports the active compound to the appropriate or desired site of action, such as oral, nasal, rectal, pulmonary, transdermal or parenteral, e.g., depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic solution, or an ointment, the parenteral or the oral route being preferred.
  • a solid carrier is used for oral administration, the preparation may be tabletted, placed in a hard gelatin capsule in powder or pellet form, or it can be in the form of a troche or lozenge.
  • the preparation may be in the form of a suspension or solution in water or a non-aqueous media, a syrup, emulsion, or soft gelatin capsules. Thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders may be added.
  • the preparation may contain a compound of formula I dissolved or suspended in a liquid carrier, in particular an aqueous carrier, for aerosol application.
  • a liquid carrier in particular an aqueous carrier
  • the carrier may contain additives such as solubilizing agents, e.g,. propylene glycol, surfactants, absorption enhancers, such as lecithin (phosphatidylcholine) or cyclodextrin, or preservatives such as parabenes.
  • solubilizing agents e.g,. propylene glycol
  • surfactants e.g. propylene glycol
  • absorption enhancers such as lecithin (phosphatidylcholine) or cyclodextrin
  • preservatives such as parabenes.
  • injectable solutions or suspensions preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil.
  • Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application.
  • Preferable carriers for tablets, dragees, or capsules include lactose, corn starch, and/or potato starch.
  • a syrup or elixir can be used in cases where a sweetened vehicle can be employed.
  • the amount of active, modified PNA molecule to be used is determined in accordance with the specific active drug, organism to be treated, and carrier of the organism.
  • “Mammals” include, but are not limited to, humans, domestic animals, such as, for example, household pets, livestock and other farm animals, and non-domestic animals, such as wildlife.
  • Dosage forms suitable for oral, nasal, pulmonal or transdermal administration comprise from about 0.01 mg to about 500 mg, preferably from about 0.01 mg to about 100 mg of the compounds of Formula I or III admixed with a pharmaceutically acceptable carrier or diluent.
  • the present invention relates to the use of one or more compounds of the general Formula I or III, or pharmaceutically acceptable salts thereof, for the preparation of a medicament for the treatment and/or prevention of infectious diseases.
  • the present invention concerns a method of treating or preventing infectious disease, comprising administering to a patient in need of treatment, or for prophylactic purposes, an effective amount of modified PNA or modified oligonucleotide according to the invention.
  • a treatment may be in the form of administering a composition in accordance with the present invention.
  • the treatment may be a combination of traditional antibiotic treatment and treatment with one or more modified PNA molecules that target genes responsible for resistance to antibiotics.
  • the phrase “effective amount” refers to that amount of modified PNA or modified oligonucleotide that is capable of abolishing, inhibiting, or retarding bacterial growth in mammals.
  • antibiotic refers to conventional antibiotics as ordinarily understood in the art, i.e., antimicrobial substances that have the ability to inhibit the growth of or to destroy microorganisms.
  • Classes of antibiotics that can be used include, but are not limited to, tetracyclines (i.e. minocycline), rifamycins (i.e. rifampin), macrolides (i.e. erythromycin), penicillins (i.e. nafcillin), cephalosporins (i.e. cefazolin), other beta-lactam antibiotics (i.e. imipenem, aztreonam), aminoglycosides (i.e.
  • gentamicin chloramphenicol, sufonamides (i.e. sulfamethoxazole), glycopeptides (i.e. vancomycin), quinolones (i.e. ciprofloxacin), fusidic acid, trimethoprim, metronidazole, clindamycin, mupirocin, polyenes (i.e. amphotericin B), azoles (i.e. fluconazole) and beta-lactam inhibitors (i.e. sulbactam).
  • antibiotics examples include, but are not limited to, minocycline, rifampin, erythromycin, nafcillin, cefazolin, imipenem, aztreonam, gentamicin, sulfamethoxazole, vancomycin, ciprofloxacin, trimethoprim, metronidazole, clindamycin, teicoplanin, mupirocin, azithromycin, clarithromycin, ofloxacin, lomefloxacin, norfloxacin, nalidixic acid, sparfloxacin, pefloxacin, amifloxacin, enoxacin, fleroxacin, temafloxacin, tosufloxacin, clinafloxacin, sulbactam, clavulanic acid, amphotericin B, fluconazole, itraconazole, ketoconazole, nystatin, and
  • the present invention also relates to a method for the disinfection of objects other than living beings, such as, for example, surgery tools, hospital inventory, dental tools, slaughterhouse inventory and tools, dairy inventory and tools, barber and beautician tools, and the like, which comprises contacting the stated objects with the modified PNA molecules and modified oligonucleotides.
  • contacting is employed in the broadest possible sense to mean any method of juxtaposition.
  • contacting the object to be disinfected with modified PNA molecules and modified oligonucleotides includes all manner of applying the modified PNA molecules and modified oligonucleotides to the object, including brushing, coating, spraying, mixing, dipping, and the like. It is also contemplated that contacting includes juxtaposition for longer or shorter periods of time.
  • linking groups are used herein: (The linking groups as starting materials are indicated with capital letters whereas the linking groups in the finished peptide-PNA conjugate are indicated with small letters.) TABLE 2 Abbreviation Linker (IUPAC) SMCC Succinimidyl 4-(N-maleimidomethyl)cyclohexane-1- carboxylate LCSMCC Succinimidyl 4-(N-maleimidomethyl)cyclohexane-1- carboxy-(6-amido-caproate) MBS Succinimidyl m-maleimido-benzoylate EMCS Succinimidyl N- ⁇ -maleimido-caproylate SMPH Succinimidyl 6-( ⁇ -maleimido-propionamido) hexanoate AMAS Succinimidyl N-( ⁇ -maleimido acetate) SMPB Succinimidyl 4-(p-maleimidophenyl)buty
  • linking groups containing a succinimidyl group are shown in FIG. 5. All the linking groups are commercially available. Mixtures of solvents are indicated on a volume basis, i.e. 30/2/10 (v/v/v).
  • Preparative HPLC was performed on a DELTA PAK (Waters)(C18, 15 ⁇ m, 300 A, 300 ⁇ 7.8 mm, 3 ml/minute).
  • the peptide-PNA-chimera H-KFFKFFKFFK-ado-TTC AAA CAT AGT-NH 2 (SEQ ID NO: 18) was synthesized on 50 mg MBHA resin (loading 100 ⁇ mol/g) (novabiochem) in a 5 ml glass reactor with a D-2 glass filter. Deprotection was performed with 2 ⁇ 600 ⁇ L TFA/m-cresol 95/5 followed by washing with DCM, DMF, 5% DIEA in DCM and DMF.
  • the coupling mixture was a 200 ⁇ l 0.26 M solution of monomer (Boc-PNA-T-monomer, Boc-PNA-A-monomer, Boc-PNA-G-monomer, Boc-PNA-C-monomer, Boc-AEEA-OH (ado) (PE Biosystems Inc.)) in NMP mixed with 200 ⁇ l 0.5 M DIEA in pyridine and activated for 1 minute with 200 ⁇ l 0.202 M HATU (PE-biosystems) in NMP.
  • the coupling mixture for the peptide part was a 200 ⁇ l 0.52 M NMP solution of amino acid (Boc-Phe-OH and Boc-Lys(2-Cl-Z)-OH (novabiochem)) mixed with 200 ⁇ l 1 M DIEA in NMP and activated for 1 minute with 200 ⁇ l 0.45 M HBTU in NMP.
  • the resin was washed with DMF, DCM, and capped with 2 ⁇ 500 ⁇ l NMP/pyridine/acetic anhydride 60/35/5. Washing with DCM, DMF and DCM terminated the synthesis cycle.
  • the oligomer was deprotected and cleaved from the resin using “low-high” TFMSA.
  • the resin was rotated for 1 hour with 2 ml of TFA/dimethylsulfid/m-cresol/TFMSA 10/6/2/0.5. The solution was removed and the resin was washed with 1 ml of TFA and 1.5 ml of TFMSA/TFA/m-cresol 2/8/1 was added. The mixture was rotated for 1.5 hours and the filtrate was precipitated in 8 ml diethylether.
  • PNA-oligomer ado-TTC AAA CAT AGT-NH 2 (SEQ ID NO: 19) (purified by HPLC) (2 mg, 0.589 ⁇ mol, MW 3396.8) was dissolved and stirred for 15 minutes in NMP:DMSO 8:2 (2 ml).
  • Succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) (PIERCE)(1.1 mg, 3.24 ⁇ mol, 5.5 eq.), dissolved in NMP (50 ⁇ l) and DIEA (34.7 ⁇ 1, 198.7 ⁇ mol), was added to the solution. The reaction mixture was stirred for 2.5 hours.
  • the product was precipitated in diethylether (10 mL) and the precipitate was washed with ether:NMP, 10:1(3 ⁇ 10 mL), and ether (3 ⁇ 10 ml). MW calculated: 3615.8 g/mol; found on MALDI: 3613.5 g/mol. The product was used without further purification.
  • This PNA is a triplex forming bis-PNA in which C (cytosine) in the “Hoogsteen strand” is exchanged with the J nucleobases (a substitute for protonated C). This substitution assures efficient triplex formation at physiological pH (Egholm, et al., Nucleic Acids Res., 1995, 23,217).
  • bacterial growth is measured by the use of a microdilution broth method according to NCCLS guidelines.
  • the present invention is not limited to this means of detecting inhibition of bacterial growth.
  • the following procedure illustrates one means for measuring bacterial growth and growth inhibition.
  • Bacterial strain E.coli K12 MG1655
  • Trays 96 well trays, Costar # 3474, Biotech Line AS, Copenhagen. (Extra low sorbent trays are used in order to prevent/minimize adhesion of PNA to tray surface).
  • a logphase culture of E.coli is diluted with fresh preheated medium and adjusted to a defined OD (here: Optical Density at 600 nm) in order to result in a final concentration of 5 ⁇ 10 5 and 5 ⁇ 10 4 bacteria/ml medium in each well, which contains 200 ⁇ l of bacterial culture.
  • PNA is added to the bacterial culture to yield final concentrations ranging from 300 nM to 1000 nM. Trays are incubated at 37° C. by shaking in a robot analyzer, PowerWave x , software KC 4, Kebo.Lab, Copenhagen, for 16 hours and optical densities are measured at 600 nM throughout the incubation in order to record growth curves. Wells containing bacterial culture without PNA are used as controls to ensure correct inoculum size and bacterial growth during the incubation. Cultures are tested in order to detect contamination.
  • the individual peptide-L-PNA constructs have molecular weights between approximately 4,200 and 5,000, depending upon the composition. All tests were therefore performed on a molar basis rather than on a weight/volume basis. Assuming an average MW of 4,500, a concentration of 500 nM equals 2.25 microgram/ml.
  • PBPs Penicillin Binding Proteins
  • the bacterial growth assay is designed to identify modified PNA molecules that inhibit or completely abolish bacterial growth. Growth inhibition results from antisense binding of PNA to mRNA of the targeted gene. The compound tested is present during the entire assay.
  • the experimental bacterial strain used is Escherichia coli K12 MG1655 ( E. coli Genentic Stock Center, Yale University, New Haven).
  • the medium for growth is 10% sterile LB (Lurea Bertani) medium.
  • E. coli test cells are pre-cultured in LB medium at 37° C. over night (over night culture).
  • the screen is performed in 96-well microtiter plates at 37° C. with constant shaking. PNAs are dissolved in H 2 O as a 40 ⁇ concentrated stock solution.
  • the test culture is diluted stepwise in the range 10 5 to 10 1 with 10% LB medium.
  • 195 ⁇ l of diluted culture and 5 ⁇ l of a 40 ⁇ concentrated PNA stock solution are added to each test well.
  • 96-well microtiter plates are incubated in a microplate scanning spectrophotometer at 37° C. under constant shaking. OD 600 measurements are performed automatically every 3.19 minutes and recorded simultaneously.
  • PBPs Penicillin Binding Proteins
  • PBPs act in the biosynthesis of murein (peptidoglycan), which is part of the envelope of Gram-positive and Gram-negative bacteria. PBPs are inhibited by the binding of penicillin, which acts as substrate analogue. Hydrolytic enzymes are activated by the accumulation of peptidoglycan intermediates and hydrolyze the peptidoglycan layer, causing lysis.
  • murein peptidoglycan
  • penicillin which acts as substrate analogue
  • Hydrolytic enzymes are activated by the accumulation of peptidoglycan intermediates and hydrolyze the peptidoglycan layer, causing lysis.
  • E.coli has 7-9 PBPs, including the high molecular weight PBPs: PBP1A and PBP1B, PBP2, and PBP3, and the low molecular weight PBPs: PBP 4-9.
  • the high molecular weight PBPs are essential for growth, whereas the low molecular weight PBPs are not.
  • PNA26 has been designed according to the sequence of the mrcA (pona) gene of E. coli , encoding PBP1A.
  • the sequence of the mrcA gene (accession number X02164) was obtained from the EMBL sequence database (Heidelberg, Germany) (Broome-Smith et al., Eur J Biochem, 1985, 147, 437).
  • the sequence of the mrcA gene is shown in FIG. 3.
  • the target region of PNA26 is the following: sense 5′AATGGGAAATTTCCA GTG AAGTTCGTAAAG3′ (SEQ ID NO: 142) 121 --------- + -------- + --------- + 150 antisense 3′TTACCCTTTAAAGGT CAC TTCAAGCATTTC5′ (SEQ ID NO: 143)
  • the coding and the non-coding (antisense) strands of the GTG start codon region are shown.
  • the sequence of the GTG start codon region of the antisense strand and PNA26 are shown in the 5′ to 3′ orientation: antisense (SEQ ID NO: 143) 5′CTTTACGAACTT CAC TGGAAATTT CCCATT3′ PNA26 (SEQ ID NO: 144) H-KFFKFFKFFK-ado- CAC TGGAAATTT -Lys-NH 2
  • PNA26 is a 12mer PNA molecule (shown in bold) coupled to a 10 amino acid peptide. Growth assay with PNA26
  • the assay was performed as follows. Dilutions of the test culture corresponding to 10 5 , 10 4 , 10 3 , 10 2 and 10 1 cells/ml containing PNA26 at a final concentration of 1.5, 2.0, 2.5, 3.0 and 3.5 ⁇ M are incubated at 37° C. for 16 hours with constant shaking. Total inhibition of growth can be seen in cultures with 10 4 -10 1 cells/ml and a PNA concentration of at least 2.5 ⁇ M (Table 6).
  • PNA14 has been designed according to the sequence of the mrdA gene encoding PBP2.
  • the sequence (accession number AE000168, bases 4051-5952) was obtained from the E. coli genome database at the NCBI (Genbank, National Centre for Biotechnology Information, USA).
  • the sequence of the mrda gene is shown in FIG. 4.
  • the target region of PNA14 is the following: sense 5′GAGTAGAAAACGCAGCGG ATG AAACTACAGAAC3′ (SEQ ID NO: 145) 99 --------- + ------ + ------ + --- 131 antisense 3′CTCATCTTTTGCGTCGCC TAC TTTGATGTCTTG5′ (SEQ ID NO: 146)
  • antisense SEQ ID NO: 146
  • 5′GTTCTGTAG TTT CAT CCGCTG CGTTTTCTACTC3′ PNA14 SEQ ID NO: 147) H-KFFKFFKFFK-ado- TTT CAT CCGCTG -Lys-NH 2
  • PNA14 is a 12mer PNA molecule (shown in bold) coupled to a 10 amino acid peptide.
  • the assay was performed as follows. Dilutions of the test culture corresponding to 10 5 , 10 4 , 10 3 , 10 2 and 10 1 cells/ml containing PNA14 at a final concentration of 1.3, 1.4 and 1.5 ⁇ M are incubated at 37° C. for 16 hours with constant shaking. Total inhibition of growth can be seen in cultures with 10 4 -10 1 cells/ml and a PNA concentration of at least 1.4 ⁇ M (Table 7).
  • Peptides are truncated versions of the KFF-motif.
  • the basic peptide sequence is KFFKFFKFFK (SEQ ID NO: 148) (PNA 1).
  • PNA 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 all contain peptides which are truncated from the C-terminal end.
  • PNA 84, 85, 86, 87, 88, 89, 90, 91 and 92 all contain peptides which are truncated from the N-terminal end.
  • the PNA targeted against the LacZ-gene has been synthesized with and without an —NH 2 terminal lysine.
  • the assay was performed as follows. Dilutions of the test culture E. coli K12 corresponding to 5 ⁇ 10 5 and 5 ⁇ 10 4 cells/ml, containing truncated versions of the KFF-motif of the PNAs targeted against the LacZ gene, at final concentrations of 100, 300, 750 and 1500 nM, were incubated in M9 minimal broth with lactose as the sole carbon source (minimal media 9, Bie & Bemtsen Cph) at 37° C. for 16 hours with constant shaking.
  • PNA 130 and PNAs 218-226, targeted against the infA-gene were synthesized with peptides which were truncated versions of the KFF-motif.
  • the assay was performed as follows. Dilutions of the test culture E. Coli K12, corresponding to 2 ⁇ 10 4 and 4 ⁇ 10 4 cells/ml, containing truncated versions of the KFF-motif in PNAs targeted against the infa-gene, at final concentrations of 200, 400, 600 800 and 1000 nM, were incubated in 10% Mueller-Hinton broth at 37° C. for 16 hours with constant shaking.
  • PNAs 140-146 targeted against the ⁇ -sarcine loop of ribosomal RNA, were synthesized with peptides which were truncated versions of the KFF-motif.
  • the assay was performed as follows. Dilutions of the test culture E. coli K12, corresponding to 2 ⁇ 10 4 and 4 ⁇ 10 4 cells/ml, containing truncated versions of the KFF-motif in PNAs targeted against the a-sarcine loop of ribosomal RNA, at final concentrations of 200, 400, 600, 800 and 1000 nM, were incubated in 10% Mueller-Hinton broth at 37° C. for 16 hours with constant shaking.
  • the assay was performed as follows. Dilutions of the test culture E. coli K12, 20 corresponding to 700 and 350 cells/ml, containing variations of amphipathic 10, 11 and 12-mer structures with smcc-linker in PNAs targeted against the FtsZ-gene, at final concentrations of 200, 300, 400, 500, 600, 800 and 1000 nM, were incubated in 100% Mueller-Hinton broth at 37° C. for 16 hours with constant shaking.
  • the experimental set-up corresponds to the set-up as described in Example 15.
  • the smcc-ado linker is the superior linker, demonstrating total inhibition of growth in cultures with 1.6 ⁇ 10 3 -8 ⁇ 10 2 cells/ml and a PNA concentration of at least 600 nM. TABLE 13 PNA conc.
  • the assay was performed as follows. Dilutions of the test culture corresponding to 10 5 , 10 4 , and 10 3 cells/ml containing peptide no. 2339 at a final concentration of 100 to 20,000 nM, were incubated at 37° C. for 16 hours with constant shaking. Total inhibition of growth was evident in cultures with 7.9 ⁇ 10 3 cells/ml and a peptide concentration of at least 20,000 nM, and minimal signs of growth inhibition were detected at concentrations from 5,000 nM (10% medium: Table 15; 100% medium: Table 16). The peptide was thus active alone, but only at very high concentrations which were above the range used for PNA growth assays. TABLE 15 Peptide conc.
  • the assay was performed as follows. Dilutions of the test culture corresponding to 10 5 , 10 4 and 10 3 cells/ml, containing PNA 136 alone or PNA 136 and peptide No. 2339 in equal amounts, at a final concentration of 400 to 1000 nM, were incubated at 37° C. for 16 hours with constant shaking. No growth inhibition was detected at any of the concentrations (Table 17). The nonsense PNA was thus not active in the chosen range. TABLE 17 PNA/Peptide conc.
  • E. coli K12 was grown in 100% Mueller-Hinton broth.
  • PNA 249 is identical to PNA 109, without the peptide but still with the ado-linker.
  • the Peptide of PNA 250 has the sequence: H-CG-KLAKALKKLL-NH 2 (SEQ ID NO: 156).
  • the peptide is also used for PNA 174.
  • PNA and peptide In the wells with both PNA and peptide there is equal amount PNA and peptide.
  • neither 249 nor 250 alone nor 249 and 250 together show any useful effect in the low concentration end. Only the peptide alone in concentrations above 2500 nM may show growth inhibition effect. TABLE 18 PNA conc.
  • E. coli K12 was grown in 10% Mueller-Hinton broth.
  • Peptides are versions of the KFF-motif placed C- or N-terminal to the PNA. From Table 19 it can be seen that both orientation of the Peptide work. However, for specific combinations of PNA and Peptide, one of the orientations may be preferred. TABLE 19 PNA conc.
  • the annotated E. faecium genome is, along with 250 other genomes, commercially available from Integrated Genomics, Chicago. Single annotated genes from both organisms are also available in Genbank.
  • PNA conjugates to inhibit bacterial growth is measured by the use of a microdilution broth method using 100% Mueller-Hinton broth, according to NCCLS Guidelines.
  • a logphase culture of E. faecium is diluted with fresh, prewarmed medium and adjusted to a defined OD (here: Optical Density at 600 nm) to yield a final concentration of 1 ⁇ 10 4 bacteria/ml medium in each well, which contain 195 ⁇ l of bacterial culture.
  • PNA is added to the bacterial culture to yield final concentrations ranging from 450 nM to 1500 nM.
  • Trays e.g. Costar #3474) are incubated at 35° C.
  • ATCC 51550 multidrugresistant (ampicillin, ciprofloxacin, gentamycin, rifampin, teicoplanin, vancomycin
  • ATCC 700221 resistant to vancomycin
  • the experimental design is as follows. MIC's were detected as previously described. Trays were incubated at 35° C. for an additional 24 hours in order to analyze regrowth of inhibited bacteria (MBC's).
  • MMC's inhibited bacteria
  • the PNA conjugate from Example 22 was used as were bacterial strains 8803, 51550, and 700221.
  • the PNA concentration in wells was 400, 800 and 1600 nM.
  • MIC MBC E. facium Strain ⁇ g/ml-(nM) ( ⁇ g/ml)-nM 8803 ⁇ 400 ⁇ 400 ATCC 51550 ⁇ 400 ⁇ 400 ATCC 700221 ⁇ 400 ⁇ 400 Peptide control >5000 >5000
  • MIC MBC E. facium Strain ⁇ g/ml-(nM) ( ⁇ g/ml)-nM 8803 ⁇ 400 ⁇ 400 ATCC 51550 ⁇ 400 ⁇ 400 ATCC 700221 ⁇ 400 ⁇ 400 Peptide control >5000 >5000
  • the ability of PNA to inhibit bacterial growth is measured by the use of a microdilution broth method using 100% Mueller-Hinton broth, according to NCCLS Guidelines.
  • a logphase culture of S aureus is diluted with fresh, pre-warmed medium and adjusted to a defined OD (here: Optical Density at 600 nm) in order to yield a final concentration of 1 ⁇ 10 4 bacteria/ml medium in each well, which contains 195 ⁇ l of bacterial culture.
  • PNA is added to the wells in order to yield final concentrations of 450 nM to 1500 nM.
  • Trays e.g. Costar #3474 are incubated at 35° C.
  • the experimental design is as follows. MIC's were detected as described above. Trays were incubated at 35° C. for an additional 24 hours in order to analyze regrowth of inhibited bacteria (MBC's).
  • the PNA from Example 24 was used as were bacterial strains 8325, 700698, and 700698R. PNA concentrations in the wells were 400, 800 and 1600 nM.
  • the Minimal Inhibitory Concentrations (MIC) were as follows: MIC MBC S.aureus Strain ⁇ g/ml (nM) ( ⁇ g/ml) nM 8325 800/1600 1600 ATCC 700698 800/1600 1600 ATCC 700698R 800/1600 ⁇ 1600
  • a compound of the invention was tested for antibacterial effect in vivo according to the test described by N. Frimodt-M ⁇ ller. Untreated animals developed fulminant clinical signs of infection. At all time points the compound of the invention suppressed the E. coli cfu/ml as compared to non-treated controls and was as efficient as the two positive controls.

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Abstract

The present invention relates to novel drugs which may be used in combating infectious micro-organisms, particularly bacteria. More specifically, the invention relates to peptide nucleic acid (PNA) sequences that are modified by conjugating cationic peptides to the PNA moiety in order to obtain novel PNA molecules that exhibit enhanced anti-infective properties

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application claims priority to Danish Application No. PA 1999 01467 filed Oct. 13, 1999; U.S. Provisional Application No. 60/159,684 filed Oct. 15, 1999; Danish Application No. PA 1999 01735 filed Dec. 3, 1999; Danish Application No. PA 2000 00522 filed Mar. 28, 2000; U.S. Provisional Application No. 60/211,758 filed Jun. 14, 2000; Danish Application No. PA 1999 01471 filed Oct. 13, 1999; U.S. Provisional Application No. 60/159,679 filed Oct. 15, 1999, Danish Application No. PA 1999 01734 filed Dec. 3, 1999; Danish Application No. PA 2000 00670 filed Apr. 19, 2000; U.S. Provisional Application No. 60/211,878 filed Jun. 14, 2000; Danish Application No. PA 2000 00671 filed Apr. 19, 2000; and U.S. Provisional Application No. 60/211,435 filed Jun. 14, 2000, each of which are incorporated herein by reference in their entirety.[0001]
    • FIELD OF THE INVENTION
  • The present invention relates to novel drugs for use in combating, for example, infectious microorganisms, particularly bacteria. More specifically, the invention relates to peptide nucleic acid (PNA) sequences that are modified in order to obtain novel PNA molecules which exhibit enhanced anti-infective properties. [0002]
    • BACKGROUND OF THE INVENTION
  • The discovery of penicillin in the 1940's marked the beginning of the search for new antibiotics. Many antibiotics have been discovered or developed from existing drugs, and the number of antibiotic drugs currently used by clinicians is more than 100. Many strains of bacteria have, unfortunately, become resistant to one or more of the currently available antibiotics. [0003]
  • Most antibiotics are products of natural microbic populations and resistant traits found in these populations can disseminate between species and appear to have been acquired by pathogens under selective pressure from antibiotics used in agriculture and medicine (Davis et al., [0004] Science, 1994, 264, 375). Antibiotic resistance may develop in bacteria harbouring genes that encode enzymes that either chemically alter or degrade antibiotics. Resistant bacteria may also encode enzymes that make the cell wall impervious to antibiotics or encode efflux pumps that eject antibiotics from the cell before the antibiotics can exert their effects. Due to the emergence of antibiotic-resistant bacterial pathogens, a need for new therapeutic strategies has arisen. One strategy for avoiding problems caused by resistance genes is the development of anti-infective drugs from novel chemical classes for which specific resistance traits do not exist.
  • Antisense agents offer a novel strategy for combatting disease, as well as opportunities to employ new chemical classes in drug design. Oligonucleotides can interact with native DNA and RNA in several ways, including duplex formation between an oligonucleotide and a single-stranded nucleic acid and triplex formation between an oligonucleotide and double-stranded DNA to form a triplex structure. The use of anti-sense methods in basic research has been encouraging, and antisense oligonucleotide drug formulations that target viral and disease-causing human genes are progressing through clinical trials. Antisense inhibition of bacterial genes could also have wide application; however, few attempts have been made to extend antisense technology to bacteria. [0005]
  • Peptide nucleic acids (PNA) are similar to oligonucleotides and oligonucleotide analogs and may mimic DNA and RNA. The deoxyribose backbone of DNA is replaced in PNA by a pseudo-peptide backbone (Nielsen et al., [0006] Science, 1991, 254, 1475; see FIG. 1). Each subunit, or monomer, has a naturally occurring or non-naturally occurring nucleobase attached to the backbone. One such backbone consists of repeating units of N-(2-aminoethyl)glycine linked through amide bonds. PNA hybridizes to complementary nucleic acids through Watson and Crick base pairing and helix formation results (Egholm et al., Nature, 1993, 365, 566). The Pseudo-peptide backbone provides superior hybridization properties (Egholm et al., Nature, 1993, 365, 566), resistance to enzymatic degradation (Demidov et al., P.E. Biochem. Pharmacol., 1994, 48, 1310) and access to a variety of chemical modifications (Nielsen et al., Chemical Society Reviews, 1997, 73).
  • PNA binds both DNA and RNA to form PNA/DNA or PNA/RNA duplexes. The resulting PNA/DNA or PNA/RNA duplexes are bound with greater affinity than corresponding DNA/DNA or DNA/RNA duplexes, as determined by T[0007] ms. The thermal stability of PNA/DNA and PNA/RNA duplexes could be due to the lack of charge repulsion in the neutral backbone of PNA. In addition to increased affinity, PNA has also been shown to hybridize to DNA with increased specificity, as compared to DNA/DNA duplexes. When a PNA/DNA duplex mismatch is melted relative to a DNA/DNA duplex, an 8 to 20° C. drop in the Tm results. Furthermore, homopyrimidine PNA oligomers form extremely stable PNA2-DNA triplexes with sequence-complementary targets in DNA or RNA oligomers. Finally, PNAs may bind to double-stranded DNA or RNA by helix invasion.
  • One advantage of PNA, as compared to oligonucleotides, is the nuclease and protease reisitance of the PNA polyamide backbone. PNA is not recognized by either nucleases or proteases and is thus not susceptible to cleavage; consequently, PNAs are resistant to degradation by enzymes, unlike nucleic acids and peptides. In antisense applications, target-bound PNA can cause steric hindrance of DNA and RNA polymerases, reverse transcripase, telomerase and ribosomes (Hanvey et al., [0008] Science, 1992, 258, 1481; Knudsen et al., Nucleic Acids Res., 1996, 24, 494; Good et al., Proc. Natl. Acad. Sci USA, 1998, 95, 2073; Good, et al., Nature Biotechnology, 1998, 16, 355).
  • A general difficulty in the use of antisense agents is cell uptake. A variety of strategies to improve uptake have been explored and reports of improved uptake into eukaryotic cells using lipids (Lewis et al., [0009] Proc. Natl. Acad. Sci. USA, 1996, 93, 3176), encapsulation (Meyer et al., J. Biol. Chem., 1998, 273, 15621) and carrier strategies (Nyce et al., Nature, 1997, 385, 721; Pooga et al., Nature Biotechnology, 1998, 16, 857) have been made. WO 99/05302 discloses a PNA conjugate consisting of PNA and the transporter peptide transportan, in which the peptide can be used for transport cross a lipid membrane and for delivery of the PNA into interactive contact with intracellular polynucleotides. U.S. Pat. No. 5,777,078 discloses a pore-forming compound which comprises a delivery agent that recognizes the target cell and is linked to a pore-forming agent, such as a bacterial exotoxin. The compound is administered together with a drug such as PNA.
  • PNAs have unique advantages as an antisense agent for microorganisms. PNA-based antisense agents can control cell growth and growth phenotypes when targeted to [0010] Escherichia coli rRNA and mRNA (Good et al., Proc. Natl. Acad. Sci USA, 1998, 95, 2073; Good et al., Nature Biotechnology, 1998, 16, 355; and WO 99/13893).
  • None of the cited disclosures discuss methods of transporting PNA across the bacterial cell wall and membrane. Poor uptake of PNA is expected because bacteria have stringent barriers against entry of foreign molecules and antisense oligomer-containing nucleobases appear to be too large for efficient uptake. The results obtained by Good and Nielsen (Good et al., [0011] Proc. Natl. Acad. Sci USA, 1998, 95, 2073; Good, et al., Nature Biotechnology, 1998, 16, 355) indicate that PNA oligomers enter bacterial cells poorly by passive diffusion across the lipid bilayers.
  • U.S. Pat. No. 5,834,430 discloses the use of potentiating agents, such as short cationic peptides, in the potentiation of antibiotics. The agent and the antibiotic are co-administered. WO 96/11205 discloses PNA conjugates, wherein a conjugated moiety may be placed on terminal or non-terminal parts of the backbone of PNA in order to functionalize the PNA. The conjugated moieties may be reporter enzymes or molecules, steroids, carbohydrate, terpenes, peptides, proteins, etc. The conjugates possess improved transfer properties for crossing cellular membranes; however, WO 96/11205 does not disclose conjugates that can cross bacterial membranes. [0012]
  • WO 98/52614 discloses a method of enhancing transport over biological membranes, e.g., a bacterial cell wall. According to this publication, biologically active agents such as PNA may be conjugated to a transporter polymer in order to enhance transmembrane transport. The transporter polymer consists of 6-25 subunits, at least 50% of which contain a guanidino or amidino side chain moiety, and wherein at least 6 contiguous subunits contain guanidino and/or amidino side chains. A preferred transporter polymer is a polypeptide containing 9-arginine. Despite the promising results obtained with the use of the PNA technology, there is a great need in the art for development of new PNA antisense drugs that are effective in combatting microorganisms. [0013]
    • SUMMARY OF THE INVENTION
  • The present invention relates to a new strategy for combatting bacteria. Antisense PNA can inhibit the growth of bacteria; however, due to slow diffusion of PNA across the bacterial cell wall, the use of PNA as an antibiotic has not been possible. According to the present invention, a practical application for PNA in combatting bacteria can be achieved by modifying the PNA through linkage of a peptide or peptide-like sequence that enhances the activity of the PNA. [0014]
  • Surprisingly, it has been demonstrated that incorporation of a peptide in PNA results in an enhanced anti-infective effect. An important feature of the modified PNA molecules is a pattern comprising positively charged and lipophilic amino acids or amino acid analogues. An anti-infective effect is found with different orientations of the peptide relative to the PNA sequence. Thus, one aspect of the present invention is directed to a modified PNA molecule, and pharmaceutically acceptable salt thereof, of Formula I: [0015]
  • Peptide-L-PNA  (I)
  • wherein L is a linker or a bond, Peptide is any amino acid sequence, and PNA is a Peptide Nucleic Acid. [0016]
  • More particularly, the present invention is directed to a modified PNA molecule of Formula I [0017]
  • Peptide-L-PNA  (I)
  • wherein Peptide is a cationic peptide or cationic peptide analogue or a functionally similar moiety, the peptide or peptide analogue having the Formula II: [0018]
  • C-(B-A)n-D,  (II)
  • wherein A is from 1 to 8 non-charged amino acids and/or amino acid analogs, B is from 1 to 3 positively charged amino acids and/or amino acid analogs, C is from 0 to 4 non-charged amino acids and/or amino acid analogs, D is from 0 to 3 positively charged amino acids and/or amino acid analogs, n is 1-10, and the total number of amino acids and/or amino acid analogs is from 3 to 20. [0019]
  • In one embodiment, the Peptide of the present invention comprises from 2 to 60 amino acids. The amino acids can be negatively charged, non-charged, or positively charged naturally-occurring, rearranged, or modified amino acids. In a preferred embodiment of the invention, the peptide comprises from 2 to 18 amino acids, and most preferably from 5 to 15 amino acids. [0020]
  • In another preferred embodiment of the invention, A in Formula II comprises from 1 to 6 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs. In another embodiment, A comprises from 1 to 4 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs. [0021]
  • In a preferred embodiment of the invention, the modified PNA molecules of Formula I are used, for example, in the treatment or prevention of infections caused by [0022] Escherichia coli or vancomycin-resistant enterococci such as Enterococcus faecalis and Enterococcus faecium or infections caused by methicillin-resistant and methicillin-vancomycin-resistant Staphylococcus aureus.
  • The peptide moiety in a modified PNA molecule is linked to the PNA sequence via the amino (N-terminal) or carboxy (C-terminal) end. In a preferred embodiment, the peptide is linked to the PNA sequence via the carboxy end. [0023]
  • In another aspect of the invention, modified PNA molecules are used in the manufacture of medicaments for the treatment or prevention of infectious diseases or for disinfecting non-living objects. In a further aspect, the invention concerns a composition for treating or preventing infectious diseases or disinfecting non-living objects. In yet another aspect, the invention concerns the treatment or prevention of infectious diseases or treatment of non-living objects. [0024]
  • In yet a further aspect, the present invention is directed to a method of identifying specific advantageous antisense PNA sequences that may be used in the modified PNA molecule according to the invention. [0025]
  • In yet a further aspect, the present invention relates to other antisense oligonucleotides with the ability to bind to both DNA and RNA. [0026]
  • Oligonucleotide analogs are oligomers having a sequence of nucleotide bases (nucleobases) and a subunit-to-subunit backbone that allows the oligomer to hybridize to a target sequence in an mRNA by Watson-Crick base pairing, to form an RNA/Oligomer duplex in the target sequence. The oligonucleotide analog may have exact sequence complementarity to the target sequence or near complementarity, as long as the hybridized duplex structure formed has sufficient stability to block or inhibit translation of the mRNA containing target sequence. [0027]
  • Oligonucleotide analogs of the present invention are selected from the group consisting of Locked Nucleoside Analogues (LNA) as described in International PCT Publication WO99/14226, oligonucleotides as described in International PCT Publication WO98/03533 or antisense oligomers, in particular morpholino analogs as described in International PCT Publication WO98/32467. [0028]
  • PCT Publication WO99/14226, WO98/03533 and WO98/32467 are all incorporated by reference. [0029]
  • Thus, further preferred compounds of the invention are modified oligonucleotides of the Formula (III): [0030]
  • Peptide-L-Oligon  (III)
  • wherein L is a linker or a bond; Peptide is any amino acid sequence and Oligon is an oligonucleotide or analog thereof.[0031]
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 shows representative chemical structures of DNA and PNA oligomers. [0032]
  • FIG. 2 is a schematic showing a representative conjugation using SMCC. [0033]
  • FIGS. 3A and 3B show the nucleotide sequence of the mrcA (ponA) gene encoding PBP1A. The sequence of the gene (accession number X02164) was obtained from the EMBL sequence database (Heidelberg, Germany) (Broome-Smith et al., [0034] Eur J Biochem, 1985, 147, 437). Two possible start codons have been identified (bolded). Bases 1-2688 are shown (ending with stop codon).
  • FIGS. 4A and 4B show the nucleotide sequence of the mrdA gene encoding PBP2. The sequence (accession number AE000168, bases 4051-5952, numbered 1-2000) was obtained from the [0035] E. coli genome database at the NCBI (Genbank, National Center for Biotechnology Information, USA). The start codon is bolded.
  • FIG. 5 shows representative chemical structures of different succinimidyl based linking groups used in conjugation of a Peptide and PNA[0036]
    • DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
  • The present invention relates, in part, to a modified oligonucleotide of Formula III: [0037]
  • Peptide-L-Oligon  (III)
  • wherein L is a linker or a bond, Peptide is any amino acid sequence, and Oligon is an oligonucleotide or analog thereof. [0038]
  • Oligons useful for the invention include, but are not limited to, oligonucleotide analogs such as, for example, Locked Nucleoside Analogues (LNA), as described in International PCT Publication WO99/14226, or analogs as described in International PCT Publication WO98/03533, or morpholino analogs as described in International PCT Publication WO98/32467, each of which are incorporated herein by reference in their entirety. [0039]
  • Antisense PNAs can inhibit bacterial gene expression with gene and sequence specificity (Good et al., [0040] Proc. Natl. Acad. Sci USA, 1998, 95, 2073; Good et al., Nature Biotechnology, 1998, 16, 355; and WO 99/13893). Antisense PNAs may prove to be a practical tool for functional genomics and a source of novel antimicrobial drugs. However, improvements in standard PNA techniques are required in order to increase antisense potencies. The major limit to antisense activity appears to be cellular entry. Bacteria effectively exclude the entry of large molecular weight foreign compounds, and previous results of in vitro and cellular assays seem to demonstrate that the cell barrier restricts antisense effects. Accordingly, the present invention concerns strategies to improve the activity of antisense PNAs.
  • Without being bound by theory, it is believed that short cationic peptides lead to improved PNA uptake over the bacterial cell wall. It is believed that the short peptides act by penetrating the cell wall and allowing the modified PNA molecule to cross the cell wall and gain access to structures inside the cell, such as the genome, mRNAs, the ribosome, etc. Improved accessibility to the nucleic acid target or improved binding of the PNA may also add to the overall effect observed. [0041]
  • According to one aspect of the invention, nanomolar concentrations of PNA molecules modified with short, activity-enhancing peptides enable specific and efficient inhibition of bacterial gene expression. Antisense potencies in this concentration range are consistent with practical applications of the technology. It is believed that the present invention demonstrates for the first time that peptides with a certain pattern of cationic and lipophilic amino acids can be used as carriers to deliver agents and other compounds into micro-organisms, such as bacteria. Further, the present invention has made it possible to administer PNA in an efficient concentration that is also acceptable to the patient. Accordingly, the present invention concerns novel modified PNA molecules of the formula: [0042]
  • Peptide-L-PNA, wherein
  • L is a linker or a bond, PNA is a peptide nucleic acid sequence, and Peptide is a cationic peptide or peptide analog or a functionally similar moiety, the peptide or peptide analog preferably having the formula: [0043]
  • C-(B-A)n-D, wherein
  • A comprises from 1 to 8 non-charged amino acids and/or amino acid analogs, B comprises from 1 to 3 positively charged amino acids and/or amino acid analogs, C comprises from 0 to 4 non-charged amino acids and/or amino acid analogs, D comprises from 0 to 3 positively charged amino acids and/or amino acid analogs, n is 1-10, and the total number of amino acids and/or amino acid analogs is from 3 to 20. [0044]
  • A preferred group of modified PNA molecules is the group wherein A comprises from 1 to 6 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs. In another preferred group, A comprises from 1 to 4 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs. [0045]
  • The terms “cationic amino acids and amino acid analogs” and “positively charged amino acids and amino acid analogs” include, but are not limited to, any natural or non-naturally occurring amino acids or amino acid analogs that have a positive charge at physiological pH. Similarly, the term “non-charged amino acids or amino acid analogs” includes any natural or non-naturally occurring amino acids or amino acid analogs that have no charge at physiological pH. Positively charged amino acids and amino acid analogs include lysine (Lys, K), arginine (Arg, R), diamino butyric acid (DAB), and ornithine (Orn). The skilled artisan is aware of further positively charged amino acids and amino acid analogs. [0046]
  • The term “cationic peptide” includes any natural or non-naturally occurring peptide that has a positive charge at physiological pH. [0047]
  • The term “peptide analog” includes any natural or non-naturally occurring peptide, or derivative thereof. [0048]
  • The non-charged amino acids and amino acid analogs include, but are not limited to, the naturally occurring amino acids alanine (Ala, A), valine (Val, V), leucine (Leu, L), isoleucine (Ile, I), proline (Pro, P), phenylanaline (Phe, F), tryptophan (Trp, W), methionine (Met, M), glycine (Gly, G), serine (Ser, S), threonine (Thr, T), cysteine (Cys, C), tyrosine (Tyr, Y), asparagine (Asn, N) and glutamine (Gln, Q), and the non-naturally occurring amino acids 2-aminobutyric acid, β-cyclohexylalanine, 4-chlorophenylalanine, norleucine and phenylglycine. The skilled artisan is aware of additional non-charged amino acids and amino acid analogs. Preferably, the non-charged amino acids and amino acid analogs are selected from the naturally occurring non-polar amino acids Ala, Val, Leu, Ile, Phe, Trp and Met or the non-naturally occurring non-polar amino acids β-cyclohexylalanine, 4-chlorophenylalanine and norleucine. [0049]
  • The term “functionally similar moiety” includes all peptide-like molecules that functionally mimic the Peptide as defined above and thus impart to the PNA molecule the same advantageous properties as the peptides comprising natural and non-natural amino acids as defined above. [0050]
  • Examples of preferred modified PNA molecules according to the invention include, but are not limited to, (Lys Phe Phe)[0051] 3 Lys-L-PNA and any subunits thereof comprising at least three amino acids. One preferred Peptide is (Lys Phe Phe)3 (SEQ ID NO: 1). Others include (Lys Phe Phe)2 Lys Phe (SEQ ID NO:2), (Lys Phe Phe)2 Lys (SEQ ID NO:157), (Lys Phe Phe)2 (SEQ ID NO:3), Lys Phe Phe Lys Phe (SEQ ID NO:4), Lys Phe Phe Lys (SEQ ID NO:5) and Lys Phe Phe. Other preferred Peptides are FFRFFRFFR (SEQ ID NO:6), LLKLLKLLK (SEQ ID NO:7), LLRLLRLLR (SEQ ID NO:8), LLKKLAKAL (SEQ ID NO:9), KRRWPWWPWKK (SEQ ID NO:10), KFKVKFVVKK (SEQ ID NO:11), LLKLLLKLLLK (SEQ ID NO:12), LLKKLAKALK (SEQ ID NO:13), and any subunits thereof comprising at least 3 amino acids whereof at least one amino acid is a positively charged amino acid. Also included are derivatives of the peptides having conservative amino acid substitutions, or insertions or deletions.
  • A third group of preferred Peptides is RRLFPWWWPFRRVC (SEQ ID NO:14), GRRWPWWPWKWPLIC (SEQ ID NO:15), LVKKVATTLKKIFSKWKC (SEQ ID NO:16), KKFKVKFVVKKC (SEQ ID NO:17) and any subunit thereof comprising at least 3 amino acids whereof at least one amino acid is a positively charged amino acid. A fourth group of preferred Peptides is magainis (Zasloff, [0052] Proc. Natl. Acad. Sci. USA, 1987, 84, 5449), for instance the synthetic magainin derivative GIGKFLHAAKKFAKAFVAEIMNS-NH2 (SEQ ID NO:158) as well as β-amino-acid oligomers (β-peptides) as described by Porter, et al., Nature, 2000, 404, 565.
  • The number of amino acids in the peptide can be from 3 to 20. Preferably, at least 3 amino acids, at least one of which is a positively charged amino acid, are necessary to obtain the advantageous effect. On the other hand, the upper limit for the number of amino acids in the peptide seems only to be set by the overall size of the PNA molecule. Preferably, the total number of amino acids is 15 or less, more preferably 12 or less, and most preferably 10 or less. [0053]
  • In a preferred embodiment of the invention, the PNA contains from 5 to 20 nucleobases, preferably from 7-15 nucleobases, and most preferably from 8 to 12 nucleobases. In a further preferred embodiment of the invention, the PNA backbone is aminoethylglycine as shown in FIG. 1. PNAs are described in, for example, WO 92/20702 and WO 92/20703, each of which is incorporated herein by reference in its entirety. [0054]
  • The PNA molecule is connected to the Peptide moiety through direct binding or through a linker. A variety of linking groups can be used to connect the PNA with the Peptide. Linking groups are described in, for example, WO 96/11205 and WO98/52614, each of which is incorporated herein by reference in its entirety. Some linking groups may be advantageous in connection with specific combinations of PNA and Peptide. [0055]
  • Preferred linking groups include 8-amino-3,6-dioxaoctanoic acid (ADO), succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), 6-aminohexanoic acid (AHEX or AHA), 4-aminobutyric acid, 4-aminocyclohexylcarboxylic acid, succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxy-(6-amido-caproate) (LCSMCC), succinimidyl m-maleimido-benzoylate (MBS), succinimidyl N-ε-maleimido-caproylate (EMCS), succinimidyl 6-(β-maleimido-propionamido) hexanoate (SMPH), succinimidyl N-(α-maleimido acetate) (AMAS), succinimidyl 4-(p-maleimidophenyl)butyrate (SMPB), β-alanine (β.ALA), Phenylglycine (PHG), 4-aminocyclohexanoic acid (ACHC), β-(cyclopropyl) alanine (β.CYPR), amino dodecanoic acid (ADC), polyethylene glycols and amino acids. Any of these groups can be used as a single linking group or together with more groups in creating a suitable linker. Further, the different linking groups can be combined in any order and number in order to obtain different functionalities in the linker arm. [0056]
  • In a preferred embodiment, the linking group is a combination of the β.ALA linking group or the ADO linking group with any of the other above mentioned linking groups. Thus, preferred linkers include, but are not limited to, -achc-β.ala-, -achc-ado-, -lcsmcc-β.ala-, -mbs-β.ala-, -emcs-β.ala-, -lcsmcc-ado-, -mbs-ado-, -emcs-ado- or -smph-ado-. Most preferred linkers include the following: -achc-β.ala-, -lcsmcc-ado- and -mbs-ado-. When succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) is used in the process of linking PNA to the peptide, it is necessary to add a cysteine (C) or a similar thiol containing moiety to the terminal end of the peptide (see FIG. 2). Additionally, amino acids, such as glycine, can be a part of the linker. The chemical structures of the different succinimidyl based linking groups used in the conjugation of the Peptide and PNA is shown in FIG. 5. [0057]
  • The Peptide is normally linked to the PNA sequence via the amino or carboxy end. However, the PNA sequence may also be linked to an internal part of the peptide, or the PNA sequence is linked to a peptide via both the amino and the carboxy end. [0058]
  • The following discussion regarding modified PNA targets is not limited to targets of modified PNA molecules and is equally applicable to targets of the modified oligonucleotides of the invention. [0059]
  • The modified PNA molecules of the present invention comprise PNA oligomer sequences that are complementary to at least one target nucleotide sequence in a microorganism, such as a bacterium. The target may be a nucleotide sequence of any RNA that is essential for the growth, and/or reproduction of the bacteria. Alternatively, the target may be a gene encoding a factor responsible for resistance to antibiotics. In a preferred embodiment, the functioning of the target nucleotide sequence is essential for the survival of the bacteria and the functioning of the target nucleic acid is blocked by the PNA sequence, in an antisense manner. [0060]
  • The binding of a PNA strand to a DNA or RNA strand can occur in one of two orientations, anti-parallel or parallel. As used in the present invention, the term “complementary” as applied to PNA does not in itself specify the orientation parallel or anti-parallel. It is significant that the most stable orientation of PNA/DNA and PNA/RNA is anti-parallel. In a preferred embodiment, PNA targeted to single-stranded RNA is complementary in an anti-parallel orientation. [0061]
  • In a another preferred embodiment of the invention, a bis-PNA consisting of two PNA oligomers covalently linked to each other is targeted to a homopurine sequence (consisting of only adenine and/or guanine nucleotides) in RNA (or DNA), with which it can form a PNA[0062] 2-RNA (PNA2-DNA) triple helix.
  • Potential target genes can be chosen based upon knowledge about bacterial physiology. A target gene can be found among those involved in one of the major process complexes: cell division, cell wall synthesis, protein synthesis (translation), nucleic acid synthesis, fatty acid metabolism, and gene regulation. A target gene can also be involved in antibiotic resistance. A further consideration in selecting target genes is that some physiological processes are primarily active in dividing cells whereas others are active under non-dividing circumstances as well. [0063]
  • Known target proteins in cell wall biosynthesis are penicillin binding proteins, PBPs, the targets of, e.g., the beta-lactam antibiotic penicillin, which are involved in the final stages of cross-linking of the murein sacculus. [0064] E. coli has 12 PBPs, which include the high molecular weight PBPs: PBP1a, PBP1b, PBP1c, PBP2 and PBP3, and seven low molecular weight PBPs: PBP 4-7, DacD, AmpC and AmpH. Only the high molecular weight PBPs are known to be essential for growth and have therefore been chosen as targets for PNA antisense molecules. Protein biosynthesis is an important process throughout the bacterial cell cycle; consequently, targeting enzymes involved in protein biosynthesis is not dependent upon cell division.
  • Proteins involved in DNA and RNA synthesis are also antibiotic targets. A target protein in DNA synthesis is gyrase, which acts in replication, transcription, repair and restriction. The enzyme consists of two subunits, both of which are candidate targets for PNA. Examples of potential targets primarily activated in dividing cells are rpoD, gyrA, gyrB, (transcription), mrcA (ponA), mrcB (ponb, pbpF), mrdA, ftsI (pbpB) (cell wall biosynthesis), ftsQ, ftsA and ftsZ (cell division). Examples of potential targets also activated in non-dividing cells are infA, infB, infC, tufA/tufB, tsf, fusA, prfA, prfB, and prfC, (translation). [0065]
  • Other potential target genes are antibiotic resistance-genes, with which the skilled artisan is familiar. Examples of such genes include, but are not limited to, genes encoding beta-lactamases and genes encoding chloramphenicol acetyl transferase. PNAs against such resistance genes could be used against resistant bacteria. [0066]
  • A further potential target gene is the acpP gene encoding the acyl carrier protein of [0067] E. Coli. ACP (acyl carrier protein) is a small and highly soluble protein, which plays a central role in type I fatty acid synthase systems. Intermediates of long chain fatty acids are covalently bound to ACP by a thioester bond between the carboxyl group of the fatty acid and the thiol group of the phosphopanthetheine prosthetic group. ACP is one of the most abundant proteins in E. coli, constituting 0.25% of the total soluble protein (ca 6×104 molecules per cell). The cellular concentration of ACP is regulated, and overproduction of ACP from an inducible plasmid is lethal to E. coli cells.
  • Infectious diseases are caused by micro-organisms including bacteria, viruses, protozoa, worms and arthropods. PNA can be modified and used to target RNA in such micro-organisms, whether the micro-organisms are sensitive or resistant to antibiotics. [0068]
  • Examples of microorganisms that can be treated in accordance with the present invention include, but are not limited to, Gram-positive bacteria such as Streptococcus, Staphylococcus, Peptococcus, Bacillus, Listeria, Clostridium, Propionebacteria; Gram-negative bacteria such as Bacteroides, Fusobacterium, Escherichia, Klebsiella, Salmonella, Shigella, Proteus, Pseudomonas, Vibrio, Legionella, Haemophilus, Bordetella, Brucella, Campylobacter, Neisseria, Branhamella; and organisms that stain poorly or not at all with Gram's stain such as Mycobacteria, Treponema, Leptospira, Borrelia, Mycoplasma, Clamydia, Rickettsia and Coxiella, [0069]
  • The incidence of multiple antimicrobial resistant bacteria that cause infections in hospitals/intensive care units is increasing. Such bacteria include methicillin-resistant and methicillin-vancomycin-resistant [0070] Staphylococcus aureus, vancomycin-resistant enterococci such as Enterococcus faecalis and Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae and cephalosporin and quinolone resistant gram negative rods (coliforms) such as E. coli, Klebsiella pneumoniae, Pseudomonas species and Enterobacter species. Recently, pan antibiotic (including carbapenems) resistant gram negative bacilli have emerged. The rapidity of the emergence of these multiple antibiotic-resistant bacteria is not being matched by the same rate of development of new antibiotics and it is, therefore, conceivable that patients with serious infections will soon no longer be treatable with currently available antimicrobials (Levy, Trends Microbial, 1996; 2, 341; Levy SB. The antibiotic paradox, how miracle drugs are destroying the miracle. New York: Plenum, 1992). Several international reports have highlighted the potential problems associated with the emergence of antimicrobial resistance in many areas of medicine and have also outlined the difficulties in the management of patients with infections caused by these micro-organisms (House of Lords Select Committee on Science and Technology. Resistance to antibiotics and other antimicrobial agents. London: HMSO, 1998; Lepellier et al., Clin Infect Dis, 1999, 3, 548).
  • Methicillin-resistant [0071] S. aureus (MRSA) (Chambers, Clin Microbiol Rev, 10, 781; Elliott, Current Medical Literature-Surgical Infections, 1997, 9), methicillin-vancomycin resistant S. aureus (VMRSA), and vancomycin resistant enterococci (VRE) have emerged as major nosocomial pathogens (House of Lords Select Committee on Science and Technology. Resistance to antibiotics and other antimicrobial agents. London: HMSO, 1998; Arthur et al., Trends Microbiol, 1996, 4, 410; Zervos, New, 1996, 4, 385; Carmelli et al., Arch Intern Med, 1999, 159, 2461). Vancomycin is currently the most reliable treatment for infections caused by MRSA, but the potential transfer of resistance genes from VRE to MRSA may leave few therapeutic options in the future. VRE provide a reservoir of vancomycin resistance genes and can also cause infections in patients with compromised immunity. Some VRE strains exhibit resistance to all major classes of antibiotic and in some hospitals in the United States VRE are responsible for more than 20% of enterococcal infections (Mcneeley et al., Pediatr Infect Dis J, 1998,17, 184; Carmelli et al., Arch Intern Med, 1999,159, 2461).
  • [0072] S. aureus, exhibiting intermediate vancomycin resistance (VISA), as well as VMRSA, have now been reported in several centers/hospitals worldwide (Johnson, J Antimicrob Chemother, 1998, 42, 289; Hiramatsu et al., Lancet, 1997, 350, 1670). Of the S. aureus isolates from the U.S.A., Europe, and Japan, 60-72% were MRSA. Multi-drug-resistant MRSA are the most common cause of surgical site infections, comprising 61% of all S. aureus infections, and are a major cause of increased morbidity and mortalityof ICU patients (Communicable Disease Report (CDN), 1999, 9, 8; Cookson, J Hosp Infec, 1999, 97; Liu et al., Chong Hua Min Kuo Hsiao Erh Ko I Hsueh Hui Tsa Chih 1993, 34, 285; Richards et al., Crit Care Med, 1999, 5, 887).
  • Coagulase negative staphylococci (CNS), such as [0073] S. epidermidis, are an important cause of infections associated with prosthetic devices and catheters (Vincent et al., LAMA, 1995, 27, 639). Although CNS display lower virulence than S aureus, they have intrinsic low-level resistance to many antibiotics, including beta-lactams and glycopeptides. In addition, many of these bacteria produce slime (biofilm), making the treatment of prosthetic associated infections difficult and often necessitating the removal of the infected prosthesis or catheter (Costerton et al., Ann Rev Microbiol., 1987, 41, 435).
  • [0074] Streptococcus pneumoniae, regarded as fully sensitive to penicillin for many years, has now acquired the genes for resistance to oral streptococci. The prevalence of these resistant strains is increasing rapidly worldwide, which will limit the therapeutic options in serious pneumococcal infections, including meningitis and pneumonia (Baquero, Microb Drug Resist, 1995, 1, 115). Streptococcus pneumoniae is the leading cause of infectious morbidity and mortality worldwide. In the U.S.A. pneumococcus is responsible for an estimated 50,000 cases of bacteremia, 3,000 cases of meningitis, 7 million cases of otitis media, and several hundred thousand cases of pneumonia. The overall yearly incidence of pneumococcal bacteremia is estimated to be 15 to 35 cases per 100,000. Current immunization of small children and the elderly have not addressed the high incidence of pneumococcal infection (Dowell, Arch Intern Med, 1999, 159, 2461; Communicable Disease Report (CDN), 1999, 10, 7; Baquero, Microb Drug Resist, 1995, 1, 115). Multi-drug resistant strains were isolated in the late 1970's and are now encountered worldwide (Baquero, Microb Drug Resist, 1995, 1, 115).
  • [0075] Pseudomonas aeruginosa, Pseudomonads species including Burkholderia cepacia and Xanthomonas malthophilia, Enterobacteriaceae including E. coli, Enterobacter species, and Klebsiella species, account for the majority of isolates in which resistance has emerged (Livermore, Commun Dis Public Health, 1998, 1, 74; Livermore, J Antimicrob Chemother, 1997, 39, 673; House of Lords Select Committee on Science and Technology. Resistance to antibiotics and other antimicrobial agents. London: HMSO, 1998). Cystitis, pneumonia, septicaemi, and postoperative sepsis are the most common types of infections. Most of the infections in intensive care unit (ICU) patients result from the patients' own endogenous flora and, in addition, up to 50% of ICU patients also acquire nosocomial infections, which are associated with a relatively high degree of morbidity and mortality (Richards et al., Crit Care Med, 1999, 5, 887; Chandrasekar et al., Crit Care Med, 1980, 15, 508; Northey et al., Surg Gynaecol Obstet, 1974, 139, 321). Microorganisms associated with these infections include Enterobacteriaceae 34%, S. aureus 30%, P. aeruginosa 29%, CNS 19% and fungi 17%.
  • Selective pressure caused by the use of broad-spectrum antibiotics has lead to multidrug resistance in Gram-negative bacteria. Each time a new drug is introduced, resistant subclones appear, and currently the majority of isolates are resistant to at least one antimicrobial (Lepellier et al., [0076] Clin Infect Dis, 1999, 3, 548; Giwercman et al., J Antimicrob Chemother, 1990, 26, 247; Livermore, Commun Dis Public Health, 1998, 1, 74; Livermore, J Antimicrob Chemother, 1997, 39, 673).
  • The low-permeability cell envelope of [0077] P. aeruginosa differs from that of E. coli. Forty-six percent of P. aeruginosa isolates from Europe are resistant to one or more antibiotic. The ability of P. aeruginosa to produce slime (biofilm), and its rapid development of resistance during treatment, often leads to therapy failure. Multidrug resistant P. aeruginosa has also become endemic within some specialized ICUs, such as those treating burns patients and cystic fibrosis patients (Hsueh et al., J Clin Microbiol, 1998, 36, 1347; Bert et al., J Antimicrob Chemother, 1996, 37, 809).
  • Several international reports have highlighted the potential problems associated with the emergence of antimicrobial resistance in the bacteria mentioned above, and it is conceivable that patients with serious infections soon will no longer be treatable with currently available antimicrobials. The increasing incidence of resistant strains among clinical isolates of [0078] S. aureus, S. epidermidis (CNS), enterococci, Streptococcus pneumoniae, gram negative bacilli (coliforms) such as E. coli, Klebsiella pneumoniae, Pseudomonas species and Enterobacter species, make these bacteria major candidates for future PNA design.
  • In another aspect of the present invention, modified PNA molecules can be used to identify preferred targets for PNAs. Using the known or partially known genome of the target micro-organisms, e.g,. from genome sequencing or cDNA libraries, different PNA sequences can be constructed and linked to an effective anti-infective enhancing Peptide and thereafter tested for anti-infective activity. It may be advantageous to select PNA sequences that are shared by as many micro-organisms as possible, or shared by a distinct subset of micro-organisms, such as, for example, Gram-negative or Gram-positive bacteria, or shared by distinct micro-organisms, or specific for a single micro-organism. [0079]
  • In one embodiment of the invention, modified PNA molecules are used for the identification of PNA sequences that are effective in blocking essential functions in bacteria. Various PNA sequences are incorporated into modified PNA molecules, which are then tested for their ability to inhibit or reduce the growth of bacteria. [0080]
  • Another embodiment of the invention involves a method of identifying PNA sequences that are useful in inhibiting or reducing the growth of one or more bacteria. The method involves mixing modified PNA molecules of Formula I, which contain different PNA sequences, with one or more bacteria. The PNA sequences are selected so as to be complementary to at least one nucleotide sequence in each bacteria. PNA sequences that are effective in inhibiting or reducing the growth of one or more bacteria are identified. [0081]
  • The compounds of Formula I can be prepared in the form of pharmaceutically acceptable salts, especially acid-addition salts, including salts of organic acids and mineral acids. The term “pharmaceutically acceptable salts” refers to derivatives of the modified PNAs of Formula I and the modified oligonucleotides of Formula III wherein the parent molecule is modified by making acid or base salts thereof. The term “pharmaceutically acceptable” refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of reasonable medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. [0082]
  • Examples of pharmaceutically acceptable salts include, but are not limited to, salts of organic acids such as formic acid, fumaric acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, succinic acid, malic acid, tartaric acid, citric acid, benzoic acid, salicylic acid, and the like. Suitable inorganic acid-addition salts include salts of hydrochloric, hydrobromic, sulphuric and phosphoric acids, and the like. Further examples of pharmaceutically acceptable inorganic or organic acid addition salts include the pharmaceutically acceptable salts listed in [0083] Journal of Pharmaceutical Science, 1977, 66, 2, which are known to the skilled artisan.
  • Pharmaceutically acceptable acid addition salts also include the hydrates that the compounds of the invention are able to form. The acid addition salts can be obtained as the direct products of compound synthesis. In the alternative, the free base can be dissolved in a suitable solvent containing the appropriate acid, and the salt isolated by evaporating the solvent or otherwise separating the salt and solvent. The compounds of this invention can form solvates with standard low molecular weight solvents using methods known to the skilled artisan. [0084]
  • In a further aspect of the present invention, the invention provides a composition for use in inhibiting growth or reproduction of infectious micro-organisms, comprising a modified PNA molecule according to the present invention. The term “composition” includes pharmaceutically acceptable compositions. [0085]
  • In one embodiment, the inhibition of the growth of micro-organisms is obtained through treatment with either the modified PNA molecule alone or in combination with antibiotics or other anti-infective agents. In another embodiment, the composition comprises two or more different modified PNA molecules. A second modified PNA molecule can be used to target the same bacteria as the first modified PNA molecule or to target different bacteria. In the latter situation, specific combinations of target bacteria may be selected for treatment. Alternatively, the target can be one or more genes that confer resistance to one or more antibiotics in one or more bacteria. In such a situation, the composition or the treatment further comprises the use of said antibiotic(s). [0086]
  • In another aspect, the present invention includes within its scope pharmaceutical compositions comprising, as an active ingredient, at least one of the compounds of the general Formula I, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent. [0087]
  • Pharmaceutical compositions of the present invention can be prepared by conventional techniques, e.g., as described in [0088] Remington: The Science and Practice of Pharmacy, 19th Ed., 1995. The compositions can appear in conventional forms, for example, capsules, tablets, aerosols, solutions, suspensions, or topical applications.
  • Typical compositions include a compound of Formula I or III, or a pharmaceutically acceptable acid addition salt thereof, associated with a pharmaceutically acceptable excipient, which may be a carrier or a diluent. The composition can be diluted by a carrier, or enclosed within a carrier that can be in the form of a capsule, sachet, paper or other container. In making the compositions, conventional techniques for the preparation of pharmaceutical compositions may be used. For example, the active compound can be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of a ampoule, capsule, sachet, paper, or other container. When the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material which acts as a vehicle, excipient, or medium for the active compound. The active compound can be adsorbed on a granular solid container, for example, in a sachet. Some examples of suitable carriers include water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatine, lactose, terra alba, sucrose, glucose, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid, or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone. [0089]
  • The carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents, thickeners or flavouring agents. The formulations of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the patient by employing procedures well known in the art. The pharmaceutical compositions can be sterilized and mixed, if desired, with auxiliary agents, emulsifiers, salt for influencing osmotic pressure, buffers and/or coloring substances, and the like, that do not deleteriously react with the active compounds. [0090]
  • The route of administration can be any route that effectively transports the active compound to the appropriate or desired site of action, such as oral, nasal, rectal, pulmonary, transdermal or parenteral, e.g., depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic solution, or an ointment, the parenteral or the oral route being preferred. If a solid carrier is used for oral administration, the preparation may be tabletted, placed in a hard gelatin capsule in powder or pellet form, or it can be in the form of a troche or lozenge. If a liquid carrier is used, the preparation may be in the form of a suspension or solution in water or a non-aqueous media, a syrup, emulsion, or soft gelatin capsules. Thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders may be added. [0091]
  • For nasal administration, the preparation may contain a compound of formula I dissolved or suspended in a liquid carrier, in particular an aqueous carrier, for aerosol application. The carrier may contain additives such as solubilizing agents, e.g,. propylene glycol, surfactants, absorption enhancers, such as lecithin (phosphatidylcholine) or cyclodextrin, or preservatives such as parabenes. For parenteral application, particularly suitable are injectable solutions or suspensions, preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil. [0092]
  • Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application. Preferable carriers for tablets, dragees, or capsules include lactose, corn starch, and/or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed. [0093]
  • In formulations for the treatment or prevention of infectious diseases in mammals, the amount of active, modified PNA molecule to be used is determined in accordance with the specific active drug, organism to be treated, and carrier of the organism. “Mammals” include, but are not limited to, humans, domestic animals, such as, for example, household pets, livestock and other farm animals, and non-domestic animals, such as wildlife. [0094]
  • Dosage forms suitable for oral, nasal, pulmonal or transdermal administration comprise from about 0.01 mg to about 500 mg, preferably from about 0.01 mg to about 100 mg of the compounds of Formula I or III admixed with a pharmaceutically acceptable carrier or diluent. [0095]
  • In a further aspect, the present invention relates to the use of one or more compounds of the general Formula I or III, or pharmaceutically acceptable salts thereof, for the preparation of a medicament for the treatment and/or prevention of infectious diseases. [0096]
  • The preceding description regarding pharmaceutically acceptable salts of modified PNA molecules and compositions comprising the modified PNA molecules of Formula I is not limited to the modified PNA molecules of Formula I and is equally applicable to the modified oligonucleotides of Formula III. [0097]
  • In yet another aspect of the present invention, the present invention concerns a method of treating or preventing infectious disease, comprising administering to a patient in need of treatment, or for prophylactic purposes, an effective amount of modified PNA or modified oligonucleotide according to the invention. Such a treatment may be in the form of administering a composition in accordance with the present invention. In particular, the treatment may be a combination of traditional antibiotic treatment and treatment with one or more modified PNA molecules that target genes responsible for resistance to antibiotics. [0098]
  • The phrase “effective amount” refers to that amount of modified PNA or modified oligonucleotide that is capable of abolishing, inhibiting, or retarding bacterial growth in mammals. [0099]
  • The term “antibiotic” refers to conventional antibiotics as ordinarily understood in the art, i.e., antimicrobial substances that have the ability to inhibit the growth of or to destroy microorganisms. Classes of antibiotics that can be used include, but are not limited to, tetracyclines (i.e. minocycline), rifamycins (i.e. rifampin), macrolides (i.e. erythromycin), penicillins (i.e. nafcillin), cephalosporins (i.e. cefazolin), other beta-lactam antibiotics (i.e. imipenem, aztreonam), aminoglycosides (i.e. gentamicin), chloramphenicol, sufonamides (i.e. sulfamethoxazole), glycopeptides (i.e. vancomycin), quinolones (i.e. ciprofloxacin), fusidic acid, trimethoprim, metronidazole, clindamycin, mupirocin, polyenes (i.e. amphotericin B), azoles (i.e. fluconazole) and beta-lactam inhibitors (i.e. sulbactam). [0100]
  • Examples of specific antibiotics that can be used include, but are not limited to, minocycline, rifampin, erythromycin, nafcillin, cefazolin, imipenem, aztreonam, gentamicin, sulfamethoxazole, vancomycin, ciprofloxacin, trimethoprim, metronidazole, clindamycin, teicoplanin, mupirocin, azithromycin, clarithromycin, ofloxacin, lomefloxacin, norfloxacin, nalidixic acid, sparfloxacin, pefloxacin, amifloxacin, enoxacin, fleroxacin, temafloxacin, tosufloxacin, clinafloxacin, sulbactam, clavulanic acid, amphotericin B, fluconazole, itraconazole, ketoconazole, nystatin, and the like. Other examples of antibiotics will readily suggest themselves to those of ordinary skill in the art. [0101]
  • The present invention also relates to a method for the disinfection of objects other than living beings, such as, for example, surgery tools, hospital inventory, dental tools, slaughterhouse inventory and tools, dairy inventory and tools, barber and beautician tools, and the like, which comprises contacting the stated objects with the modified PNA molecules and modified oligonucleotides. [0102]
  • As used herein, the term “contacting” is employed in the broadest possible sense to mean any method of juxtaposition. Thus, contacting the object to be disinfected with modified PNA molecules and modified oligonucleotides includes all manner of applying the modified PNA molecules and modified oligonucleotides to the object, including brushing, coating, spraying, mixing, dipping, and the like. It is also contemplated that contacting includes juxtaposition for longer or shorter periods of time. [0103]
    • EXAMPLES
  • The following examples are merely illustrative of the present invention and should not be considered as limiting of the scope of the invention in any way. The principle of the present invention is shown using [0104] E. coli as a test organism. However, as shown in Example 19, the advantageous effect applies in the same way to other bacteria. Additional objects, features, and advantages of the invention will be apparent from the following description of the presently preferred embodiments.
  • The following abbreviations related to reagents are used herein: (The monomers and the PNA sequences are stated in bold) [0105]
    TABLE 1
    A monomer N-(2-Boc-aminoethyl)-N-(N6-(benzyloxycarbonyl)
    adenine-9-yl-acetyl)glycine
    Boc Tert butyloxycarbonyl
    Boc- N-α-Boc-N-ε-2-chlorobenzyloxycarbonyl-L-lysine
    Lys(2-Cl-Z)-OH
    C monomer N-(2-Boc-aminoethyl)-N-(N4-(benzyloxycarbonyl)
    cytosine-1-yl-acetyl)glycine
    DCM Dichloromethane
    DIEA N,N-diisopropylethylamine
    DMF N,N-dimethylformamide
    DMSO Dimethyl sulfoxide
    G monomer N-(2-Boc-aminoethyl)-N-(N2-(benzyloxycarbonyl)
    guanine-9-yl-acetyl)glycine
    HATU N-[(1-H-benzotriazole-1-yl)(dimethylamine)
    methylene]-N-
    methylmethanaminiuimhexafluorophosphate
    N-oxide
    HBTU 2-(1-H-benzotriazole-1-yl)-1,1,3,
    3-tetramethyluronium hexafluorophosphate
    J monomer N-(2-Boc-aminoethyl)-N-(N-2-(benzyloxycarbonyl)
    /nucleobase isocytosine-5-yl-acetyl)glycine
    MBHA resin p-methylbenzhydrylamine resin
    NMP N-methyl pyrrolidone
    T monomer N-(2-Boc-aminoethyl)-N-(thymine-1-yl-acetyl)
    glycine
    TFA Trifluoroacetic acid
    TFSMA Trifluoromethanesulphonic acid
    Tris 2-amino-2-(hydroxymethyl)-1,3-propanediol
  • The following abbreviations relating to linking groups are used herein: (The linking groups as starting materials are indicated with capital letters whereas the linking groups in the finished peptide-PNA conjugate are indicated with small letters.) [0106]
    TABLE 2
    Abbreviation Linker (IUPAC)
    SMCC Succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-
    carboxylate
    LCSMCC Succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-
    carboxy-(6-amido-caproate)
    MBS Succinimidyl m-maleimido-benzoylate
    EMCS Succinimidyl N-ε-maleimido-caproylate
    SMPH Succinimidyl 6-(β-maleimido-propionamido)
    hexanoate
    AMAS Succinimidyl N-(α-maleimido acetate)
    SMPB Succinimidyl 4-(p-maleimidophenyl)butyrate
    b.ALA β-alanine
    PHG Phenylglycine
    ACHC 4-aminocyclohexanoic acid
    b.CYPR β-(cyclopropyl) alanine
    AHA, AHEX 6-amino-hexanoic acid
    ADO, AEEA-OH ((2-aminoethoxy)ethoxy)acetic acid or 8-amino-3,
    6-dioxaoctanoic acid
    ADC Amino dodecanoic acid
  • General Procedures [0107]
  • The linking groups containing a succinimidyl group are shown in FIG. 5. All the linking groups are commercially available. Mixtures of solvents are indicated on a volume basis, i.e. 30/2/10 (v/v/v). [0108]
  • Preparative HPLC was performed on a DELTA PAK (Waters)(C18, 15 μm, 300 A, 300×7.8 mm, 3 ml/minute). A linear gradient from solvent A: 0.1% TFA in water to B: 0.1% TFA in acetonitrile was used. 0-2 minutes B 10%, 2-30 minutes 40% B, 30-35 minutes 100% B, 35-37 minutes 100% B, 37-38 minutes 10% B, 37-50 minutes 10% B. [0109]
  • Mass Spectrometry was performed on MALDI (Matrix Assisted Laser Desorption and lonisation Time of Flight Mass Spectrometry) as HP MALDI-TOF # G2025A calibrated with peptide nucleic acids of the following weights: MW1=1584.5 g/mol, MW[0110] 2=3179.0 g/mol and MW3=4605.4 g/mol.
    • Example 1 Preparation of H-KFFKFFKFFK-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO 18)
  • The peptide-PNA-chimera H-KFFKFFKFFK-ado-TTC AAA CAT AGT-NH[0111] 2 (SEQ ID NO: 18) was synthesized on 50 mg MBHA resin (loading 100 μmol/g) (novabiochem) in a 5 ml glass reactor with a D-2 glass filter. Deprotection was performed with 2×600 μL TFA/m-cresol 95/5 followed by washing with DCM, DMF, 5% DIEA in DCM and DMF. The coupling mixture was a 200 μl 0.26 M solution of monomer (Boc-PNA-T-monomer, Boc-PNA-A-monomer, Boc-PNA-G-monomer, Boc-PNA-C-monomer, Boc-AEEA-OH (ado) (PE Biosystems Inc.)) in NMP mixed with 200 μl 0.5 M DIEA in pyridine and activated for 1 minute with 200 μl 0.202 M HATU (PE-biosystems) in NMP. The coupling mixture for the peptide part was a 200 μl 0.52 M NMP solution of amino acid (Boc-Phe-OH and Boc-Lys(2-Cl-Z)-OH (novabiochem)) mixed with 200 μl 1 M DIEA in NMP and activated for 1 minute with 200 μl 0.45 M HBTU in NMP. After coupling, the resin was washed with DMF, DCM, and capped with 2×500 μl NMP/pyridine/acetic anhydride 60/35/5. Washing with DCM, DMF and DCM terminated the synthesis cycle. The oligomer was deprotected and cleaved from the resin using “low-high” TFMSA. The resin was rotated for 1 hour with 2 ml of TFA/dimethylsulfid/m-cresol/TFMSA 10/6/2/0.5. The solution was removed and the resin was washed with 1 ml of TFA and 1.5 ml of TFMSA/TFA/m-cresol 2/8/1 was added. The mixture was rotated for 1.5 hours and the filtrate was precipitated in 8 ml diethylether.
  • The precipitate was washed with 8 ml of diethylether. The crude oligomer was dissolved in water and purified by HPLC. Preparative HPLC was performed on a DELTA PAK (Waters) (C18, 15 μm, 300 Å, 300×7.8 mm, 3 ml/minute) A linear gradient from solvent A: 0.1% TFA in water to B: 0.1% TFA in acetonitrile was used. 0-2 minutes B 10%, 2-30 minutes 40% B, 30-35 minutes 100% B, 35-37 minutes 100% B, 37-38 minutes 10% B, 37-50 minutes 10% B. MW calculated: 4791.9 g/mol; found on MALDI: 4791 g/mol. [0112]
    • Example 2 Maleimide activation of PNA
  • PNA-oligomer ado-TTC AAA CAT AGT-NH[0113] 2 (SEQ ID NO: 19) (purified by HPLC) (2 mg, 0.589 μmol, MW 3396.8) was dissolved and stirred for 15 minutes in NMP:DMSO 8:2 (2 ml). Succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) (PIERCE)(1.1 mg, 3.24 μmol, 5.5 eq.), dissolved in NMP (50 μl) and DIEA (34.7 μ1, 198.7 μmol), was added to the solution. The reaction mixture was stirred for 2.5 hours. The product was precipitated in diethylether (10 mL) and the precipitate was washed with ether:NMP, 10:1(3×10 mL), and ether (3×10 ml). MW calculated: 3615.8 g/mol; found on MALDI: 3613.5 g/mol. The product was used without further purification.
    • Example 3 Conjugation of Peptide and Maleimide Activated PNA
  • A solution of peptide CKFFKFFKFFK (SEQ ID NO: 20) (0.5 mg in 200 μl degassed Tris buffer 10 mM, pH 7.6 (329 nM)) was added to a solution of the above activated product (0.2 mg in 200 μl DMF:Water 1:1). The reaction mixture was stirred overnight. The target compound was purified by HPLC directly from the crude reaction mixture. Preparative HPLC was performed on a DELTA PAK (Waters) (C18, 15 μm, 300 Å, 300×7.8 mm, 3 ml/minute) A linear gradient from solvent A: 0.1% TFA in water to B: 0.1% TFA in acetonitrile was used. 0-2 minutes B 10%, 2-30 minutes 40% B, 30-35 minutes 100% B, 35-37 minutes 100% B, 37-38 minutes 10% B, 37-50 minutes 10% B. MW calculated: 5133.0 g/mol; found on MALDI: 5133 g/mol. [0114]
    • Example 4 Preparation of H-LLKKLAKALKG-ahex-ado-CCATCTAATCCT-NH2 (SEQ ID NO: 21)
  • Preparation of H-LLKKLAKALKG-ahex-ado-CCATCTAATCCT-NH[0115] 2 (SEQ ID NO: 21) was performed in accordance with example 1, except 6-aminohexanoic acid (ahex) and 8-amino-3,6-dioxaoctanoic acid (ado) were used as linkers.
    • Example 5 Preparation of H-KFFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCCTCTC-Lys-NH2 (SEQ ID NO: 22)
  • Preparation of H-KFFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCCTCTC-Lys-NH[0116] 2 (SEQ ID NO: 22) was performed in accordance with example 1, except PNA oligomer ado-JTJTJJT-ado-ado-ado-TCCCTCTC-Lys-NH2 (SEQ ID NO: 23) was used instead of ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 19). This PNA is a triplex forming bis-PNA in which C (cytosine) in the “Hoogsteen strand” is exchanged with the J nucleobases (a substitute for protonated C). This substitution assures efficient triplex formation at physiological pH (Egholm, et al., Nucleic Acids Res., 1995, 23,217).
    • Example 6 Preparation of Peptide-PNA-Chimeras
  • The following peptide-PNA-chimeras were prepared as described above. [0117]
    TABLE 3
    1 H-KFFKFFKFFK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 24)
    2 H-FFKFFKFFK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 25)
    3 H-FKFFKFFK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 26)
    4 H-KFFKFFK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 27)
    5 H-FFKFFK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 28)
    6 H-FKFFK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 29)
    7 H-KFFK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 30)
    8 H-FFK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 31)
    9 H-FK-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 32)
    10 H-K-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 33)
    11 H-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 34)
    84 H-KFFKFFKFF-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 35)
    85 H-FFKFFKFF-ado-CAT AGC TGT TTC-NH2 (SEQ lID NO: 36)
    86 H-FKFFKFF-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 37)
    87 H-KFFKFF-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 38)
    88 H-FFKFF-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 39)
    89 H-FKFF-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 40)
    90 H-KFF-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 41)
    91 H-FF-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 42)
    92 H-F-ado-CAT AGC TGT TTC-NH2 (SEQ ID NO: 43)
    109 H-KFFKFFKFFK-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 18)
    136 H-KFFKFFKFFK-ado-TGA CTA GAT GAG-NH2 (SEQ ID NO: 44)
    130 H-KFFKFFKFFK-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 45)
    140 H-KFF-ado-JTJTJJT-ado-ado-ado-TCC TCT C-Lys-NH2 (SEQ ID NO: 46)
    141 H-FKFF-ado-JTJTJJT-ado-ado-ado-TCC TCT C-Lys-NH2 (SEQ ID NO: 47)
    142 H-FFKFF-ado-JTJTJJT-ado-ado-ado-TCC TCT C-Lys-NH2 (SEQ ID NO: 48)
    143 H-KFFKFF-ado-JTJTJJT-ado-ado-ado-TCC TCT C-Lys-NH2 (SEQ ID NO: 49)
    144 H-FKFFKFF-ado-JTJTJJT-ado-ado-ado-TCC TCT C-Lys-NH2 (SEQ ID NO: 50)
    145 H-FFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCC TCT C-Lys-NH2 (SEQ ID NO: 51)
    146 H-KFFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCC TCT C-Lys-NH2 (SEQ ID NO: 52)
    170 H-FFKFFKFFK-GGC-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 53)
    171 H-FFRFFRFFR-GGC-smcc-ado-TTC AAA CAT AGT-NHhd 2 (SEQ ID NO: 54)
    172 H-LLKLLKLLK-GGC-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 55)
    173 H-LLRLLRLLR-GGC-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 56)
    174 H-LLKKLAKALK-GC-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 57)
    175 H-KRRWPWWPWKK-C-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 58)
    176 H-KFKVKFVVKK-GC-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 59)
    177 H-LLKLLLKLLLK-C-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 60)
    178 H-FFKFFKFFK-GGC-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 61)
    179 H-KFFKFFKFFK-C-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 62)
    218 H-F-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 63)
    219 H-FF-ado-CCA TCT AAT CCT-N2 (SEQ ID NO: 64)
    220 H-KEF-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 65)
    221 H-FKFF-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 66)
    222 H-FFKFF-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 67)
    223 H-KFFKFF-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 68)
    224 H-FKFFKFF-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 69)
    225 H-FFKFFKFF-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 70)
    226 H-KFFKFFKFF-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 71)
    228 H-LLKKLAKALKG-ahex-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 21)
    229 H-LLKKLAKALKG-ado-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 72)
    230 H-KFFKFFKFFK-ado-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 73)
    231 H-KFFKFFKFFK-ahex-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 74)
    232 H2N-KFFKFFKFFK-C-smcc-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 75)
    233 H2N-LLKKLAKALK-GC-smcc-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 76)
    234 H2N-KFFKFF-C-smcc-ado-CCA TCT AAT CCT-NH2 (SEQ ID NO: 77)
    249 H-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 78)
    371 H2N-KFFKVKFVVKK-C-smcc-ado-TTC AAA CAT AGT-NH2 (SEQ ID NO: 79)
    381 H2N-KFFKVKFVVKK-C-smcc-ado-TTG TGC CCC GTC-NH2 (SEQ ID NO: 80)
    • Example 7 Preparation of Peptide-PNA Chimeras
  • The peptide-PNA-chimeras listed in Table 4 were prepared as described in Example 1 using the linking groups as defined above. [0118]
    TABLE 4
    PA
    no. Sequence MW
    437 H2N-KKFKVKFVVKKC-achc-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO: 81) 4808
    432 H-KFFKFFKFFK-achc-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO: 82) 4848
    418 H2N-KKFKVKFVVKKC-lcsmcc-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 83) 5203
    419 H2N-KKFKVKFVVKKC-mbs-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 84) 5070
    420 H2N-KKFKVKFVVKKC-emcs-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 85) 5064
    421 H2N-KKFKVKFVVKKC-smph-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 86) 5135
    422 H2N-KKFKVKFVVKKC-amas-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 87) 5008
    423 H2N-KKFKVKFVVKKC-smpβ-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 88) 5112
    446 H2N-KKFKVKFVVKKC-lcsmcc-gly-TTCAAACATAGT-NH2 (SEQ ID NO: 89) 5109
    447 H2N-KKFKVKFVVKKC-lcsmcc-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO:90) 5121
    448 H2N-KKFKVKFVVKKC-lcsmcc-β.cypr-TTCAAACATAGT-NH2 (SEQ ID NO: 91) 5147
    449 H2N-KKFKVKFVVKKC-lcsmcc-aha-TTCAAACATAGT-NH2 (SEQ ID NO: 92) 5163
    450 H2N-KKFKVKFVVKKC-lcsmcc-adc-TTCAAACATAGT-NH2 (SEQ ID NO: 93) 5247
    • Example 8 Preparation of Peptide-DNA Chimeras
  • The peptide-PNA-chimeras listed in Table 5 were prepared as described in Example 1 using the linking groups as defined above. [0119]
    TABLE 5
    PA no. Mw Sequence
    S 201 4943,30 H-KFFKFFKFFK-ado-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 94)
    S 202 4841,40 H-KFFKFFKFFK-ado-Gly-TTCAAACATAGT-NH2 (SEQ ID NO: 95)
    S 203 4881,40 H-KFFKFFKLFFK-ado-P-TTCAAACATAGT-NH2 (SEQ ID NO: 96)
    S 204 4897,50 H-KFFKFFKFFK-ado-aha-TTCAAACATAGT-NH2 (SEQ ID NO: 97)
    S 205 4855,40 H-KFFKFFKFFK-ado-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO: 98)
    S 206 4909,50 H-KFFKFFKFFK-ado-achc-TTCAAACATAGT-NH2 (SEQ ID NO: 99)
    S 207 4841,40 H-KFFKFFKFFK-Gly-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 100)
    S 208 4765,40 H-KFFKFFKFFK-Gly-Gly-TTCAAACATAGT-NH2 (SEQ ID NO: 101)
    S 209 4805,50 H-KFFKFFKFFK-Gly-P-TTCAAACATAGT-NH2 (SEQ ID NO: 102)
    S 210 4821,50 H-KFFKFFKFFK-Gly-aha-TTCAAACATAGT-NH2 (SEQ ID NO: 103)
    S 211 4779,40 H-KFFKFFKFFK-Gly-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO: 104)
    S 212 4833,50 H-KFFKFFKFFK-Gly-achc-TTCAAACATAGT-NH2 (SEQ ID NO: 105
    S 213 4881,40 H-KFFKFFKFFK-P-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 106)
    S 214 4805,50 H-KFFKFFKFFK-P-Gly-TTCAAACATAGT-NH2 (SEQ ID NO: 107)
    S 215 4845,50 H-KFFKFFKFFK-P-P-TTCAAACATAGT-NH2 (SEQ ID NO: 108)
    S 216 4861,60 H-KFFKFFKFFK-P-aha-TTCAAACATAGT-NH2 (SEQ ID NO: 109)
    S 217 4819,50 H-KFFKFFKFFK-P-β.ala-TTCAAACATAGT-NH 2 (SEQ ID NO: 110)
    S 218 4873,60 H-KFFKFFKFFK-P-achc-TTCAAACATAGT-NH2 (SEQ ID NO: 111)
    S 219 4897,50 H-KFFKFFKFFK-aha-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 112)
    S 220 4821,50 H-KFFKFFKFFK-aha-Gly-TTCAAACATAGT-NH2 (SEQ ID NO: 113)
    S 221 4861,60 H-KFFKFFKFFK-aha-P-TTCAAACATAGT-NH2 (SEQ ID NO: 114)
    S 222 4877,60 H-KFFKFFKFFK-aha-aha-TTCAAACATAGT-NH2 (SEQ ID NO: 115)
    S 223 4835,50 H-KFFKFFKFFK-aha-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO:116)
    S 224 4889,70 H-KFFKFFKFFK-aha-achc-TTCAAACATAGT-NH2 (SEQ ID NO:117)
    S 225 4855,40 H-KFFKFFKFFK-β.ala-ado-TTCAAACATAGT-NH2 (SEQ ID NO:118)
    S 226 4779,40 H-KFFKFFKFFK-β.ala-Gly-TTCAAACATAGT-NH2 (SEQ ID NO: 119)
    S 227 4819,50 H-KFFKFFKFFK-β.ala-P-TTCAAACATAGT-NH2 (SEQ ID NO: 120)
    S 228 4835,50 H-KFFKFFKFFK-β.ala-aha-TTCAAACATAGT-NH2 (SEQ ID NO:121)
    S 229 4793,50 H-KFFKFFKFFK-β.ala-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO: 122)
    S 230 4847,60 H-KFFKFFKFFK-β.ala-achc-TTCAAACATAGT-NH2 (SEQ ID NO: 123)
    S 231 4845,50 H-KFFKFFKFFK-P-p-TTCAAACATAGT-NH2 (SEQ ID NO: 124)
    S 232 4845,50 H-KFFKFFKFFK-P-P-TTCAAACATAGT-NH2 (SEQ ID NO: 125)
    S 233 4907,70 H-KFFKFFKFFK-K-K-TTCAAACATAGT-NH2 (SEQ ID NO: 126)
    S 234 4945,70 H-KFFKFFKFFK-F-F-TTCAAACATAGT-NH2 (SEQ ID NO: 127)
    S 235 4926,60 H-KFFKFFKFFK-F-K-TTCAAACATAGT-NH2 (SEQ ID NO: 128)
    S 236 4926,60 H-KFFKFFKFFK-K-F-TTCAAACATAGT-NH2 (SEQ ID NO: 129)
    S 237 4917,50 H-KFFKFFKFFK-phg-ado-TTCAAACATAGT-NH2 (SEQ ID NO: 130)
    S 238 4841,50 H-KFFKFFKFFK-phg-Gly-TTCAAACATAGT-NH2 (SEQ ID NO: 131)
    S 239 4881,60 H-KFFKFFKFFK-phg-P-TTCAAACATAGT-NH2 (SEQ ID NO: 132)
    S 240 4897,60 H-KFFKFFKFFK-phg-aha-TTCAAACATAGT-NH2 (SEQ ID NO: 133)
    S 241 4855,50 H-KFFKFFKFFK-phg-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO: 134)
    S 242 4909,60 H-KFFKFFKFFK-phg-achc-TTCAAACATAGT-NH2 (SEQ ID NO:135)
    S 243 4909,50 H-KFFKFFKFFK-achc-ado-TTCAAACATAGT-NH2 (SEQ ID NO:136)
    S 244 4833,50 H-KFFKFFKFFK-achc-Gly-TTCAAACATAGT-NH2 (SEQ ID NO:137)
    S 245 4873,60 H-KFFKFFKFFK-achc-P-TTCAAACATAGT-NH2 (SEQ ID NO: 138)
    S 246 4889,60 H-KFFKFFKFFK-achc-aha-TTCAAACATAGT-NH2 (SEQ ID NO:139)
    S 247 4847,60 H-KFFKFFKFFK-achc-β.ala-TTCAAACATAGT-NH2 (SEQ ID NO: 140)
    S 248 4901,70 H-KEFKFFKFFK-achc-achc-TTCAAACATAGT-NH2 (SEQ ID NO: 141)
    • Example 9 Measurement of Bacterial Growth and Growth Inhibition
  • The ability of the compounds of the present invention to inhibit bacterial growth can be measured in many ways, which are clear to the skilled artisan. For the purpose of exemplifying the present invention, bacterial growth is measured by the use of a microdilution broth method according to NCCLS guidelines. The present invention is not limited to this means of detecting inhibition of bacterial growth. The following procedure illustrates one means for measuring bacterial growth and growth inhibition. [0120]
  • Bacterial strain: [0121] E.coli K12 MG1655
  • Media: [0122]
  • 10% Mueller-Hinton broth, diluted with sterile water. [0123]
  • 10% LB broth, diluted with sterile water. [0124]
  • 100% Mueller-Hinton broth. [0125]
  • Trays: 96 well trays, Costar # 3474, Biotech Line AS, Copenhagen. (Extra low sorbent trays are used in order to prevent/minimize adhesion of PNA to tray surface). [0126]
  • A logphase culture of [0127] E.coli is diluted with fresh preheated medium and adjusted to a defined OD (here: Optical Density at 600 nm) in order to result in a final concentration of 5×105 and 5×104 bacteria/ml medium in each well, which contains 200 μl of bacterial culture. PNA is added to the bacterial culture to yield final concentrations ranging from 300 nM to 1000 nM. Trays are incubated at 37° C. by shaking in a robot analyzer, PowerWavex, software KC4, Kebo.Lab, Copenhagen, for 16 hours and optical densities are measured at 600 nM throughout the incubation in order to record growth curves. Wells containing bacterial culture without PNA are used as controls to ensure correct inoculum size and bacterial growth during the incubation. Cultures are tested in order to detect contamination.
  • The individual peptide-L-PNA constructs have molecular weights between approximately 4,200 and 5,000, depending upon the composition. All tests were therefore performed on a molar basis rather than on a weight/volume basis. Assuming an average MW of 4,500, a concentration of 500 nM equals 2.25 microgram/ml. [0128]
  • Growth Inhibitory Effect of PNA-Constructs: [0129]
  • Bacterial growth is described by the lag phase, i.e., the period until (before) growth starts, the log phase, i.e., the period with maximal growth rate, the steady-state phase, and finally the death phase. These parameters are used to evaluate the inhibitory (Minimal Inhibitory Concentration, abbr. MIC) and bactericidal (Minimal Bactericidal Concentration, abbr. MBC) effect of PNA on bacterial growth by comparing growth curves with and without PNA. Total inhibition of bacterial growth is defined as: OD (16 hours)=OD (0 hours,) or no visible growth, according to NCCLS Guidelines [0130]
  • In an initial screen modified PNA molecules are tested in the sensitive 10% medium assay. Positive results are then run in the 100% medium assay in order to verify the inhibitory effect in a more “real” environment (cf. the American guidelines (NCCLS)). [0131]
    • Example 10 Measurement of in vivo Antibacterial Efficacy
  • In vivo antibacterial efficacy is established by testing a compound of the invention in the mouse peritonitis/sepsis model as described by N. Frimodt-Møller et al., 1999, Chap. 14, Handbook of Animal Models of Infection. A number of female NMRI mice are inoculated with 10[0132] 7 cfu of E. coli ATCC 25922 intraperitoneally. At one hour post-infection the mice are treated once in groups with: 1) Gentamycin (38 mg/kg s.c.); 2) Ampicillin (550 mg/kg s.c.); 3) a compound of the invention (50-60 mg/kg i.v.); and 4) no treatment. Samples are drawn from blood and peritoneal fluid at 1, 2, 4, and 6 hours post infection, and cfu/ml are counted.
    • Example 11 Bacterial Growth Inhibition with PNAs Targeted Against Penicillin Binding Proteins (PBPs)
  • Description of a Primary Screen [0133]
  • The bacterial growth assay is designed to identify modified PNA molecules that inhibit or completely abolish bacterial growth. Growth inhibition results from antisense binding of PNA to mRNA of the targeted gene. The compound tested is present during the entire assay. [0134]
  • Components [0135]
  • The experimental bacterial strain used is [0136] Escherichia coli K12 MG1655 (E. coli Genentic Stock Center, Yale University, New Haven). The medium for growth is 10% sterile LB (Lurea Bertani) medium. E. coli test cells are pre-cultured in LB medium at 37° C. over night (over night culture). The screen is performed in 96-well microtiter plates at 37° C. with constant shaking. PNAs are dissolved in H2O as a 40×concentrated stock solution.
  • Assay Conditions [0137]
  • A fresh culture (test culture) is inoculated with an overnight culture and grown to mid-log-phase (OD[0138] 600=0.1 corresponding to 107 cells/ml) at 37° C. The test culture is diluted stepwise in the range 105 to 101 with 10% LB medium. 195 μl of diluted culture and 5 μl of a 40×concentrated PNA stock solution are added to each test well. 96-well microtiter plates are incubated in a microplate scanning spectrophotometer at 37° C. under constant shaking. OD600 measurements are performed automatically every 3.19 minutes and recorded simultaneously.
  • Target Genes: [0139]
  • Penicillin Binding Proteins (PBPs) [0140]
  • PBPs act in the biosynthesis of murein (peptidoglycan), which is part of the envelope of Gram-positive and Gram-negative bacteria. PBPs are inhibited by the binding of penicillin, which acts as substrate analogue. Hydrolytic enzymes are activated by the accumulation of peptidoglycan intermediates and hydrolyze the peptidoglycan layer, causing lysis. [0141]
  • [0142] E.coli has 7-9 PBPs, including the high molecular weight PBPs: PBP1A and PBP1B, PBP2, and PBP3, and the low molecular weight PBPs: PBP 4-9. The high molecular weight PBPs are essential for growth, whereas the low molecular weight PBPs are not.
  • PNA Design No. 1 [0143]
  • PNA26 has been designed according to the sequence of the mrcA (pona) gene of [0144] E. coli, encoding PBP1A. The sequence of the mrcA gene (accession number X02164) was obtained from the EMBL sequence database (Heidelberg, Germany) (Broome-Smith et al., Eur J Biochem, 1985, 147, 437). The sequence of the mrcA gene is shown in FIG. 3.
  • The target region of PNA26 is the following: [0145]
    sense 5′AATGGGAAATTTCCAGTGAAGTTCGTAAAG3′ (SEQ ID NO: 142)
    121 ---------+--------+---------+ 150
    antisense 3′TTACCCTTTAAAGGTCACTTCAAGCATTTC5′ (SEQ ID NO: 143)
  • The coding and the non-coding (antisense) strands of the GTG start codon region are shown. The sequence of the GTG start codon region of the antisense strand and PNA26 are shown in the 5′ to 3′ orientation: [0146]
    antisense (SEQ ID NO: 143)
    5′CTTTACGAACTT CACTGGAAATTTCCCATT3′
    PNA26 (SEQ ID NO: 144)
    H-KFFKFFKFFK-ado- CACTGGAAATTT-Lys-NH2
  • PNA26 is a 12mer PNA molecule (shown in bold) coupled to a 10 amino acid peptide. Growth assay with PNA26 [0147]
  • The assay was performed as follows. Dilutions of the test culture corresponding to 10[0148] 5, 104, 103, 102 and 101 cells/ml containing PNA26 at a final concentration of 1.5, 2.0, 2.5, 3.0 and 3.5 μM are incubated at 37° C. for 16 hours with constant shaking. Total inhibition of growth can be seen in cultures with 104-101 cells/ml and a PNA concentration of at least 2.5 μM (Table 6).
  • PNA Design No. 2 [0149]
  • PNA14 has been designed according to the sequence of the mrdA gene encoding PBP2. The sequence (accession number AE000168, bases 4051-5952) was obtained from the [0150] E. coli genome database at the NCBI (Genbank, National Centre for Biotechnology Information, USA). The sequence of the mrda gene is shown in FIG. 4.
  • The target region of PNA14 is the following: [0151]
    sense 5′GAGTAGAAAACGCAGCGGATGAAACTACAGAAC3′ (SEQ ID NO: 145)
    99 ---------+---------+---------+--- 131
    antisense 3′CTCATCTTTTGCGTCGCCTACTTTGATGTCTTG5′ (SEQ ID NO: 146)
  • Both the coding (sense) and the non-coding (antisense) strand of the GTG start codon region are shown. [0152]
  • In the following sequence of the ATG start codon region of the antisense strand and PNA26 are shown in the 5′ to 3′ orientation: [0153]
    antisense (SEQ ID NO: 146)
    5′GTTCTGTAGTTTCATCCGCTGCGTTTTCTACTC3′
    PNA14 (SEQ ID NO: 147)
    H-KFFKFFKFFK-ado-TTTCATCCGCTG-Lys-NH2
  • PNA14 is a 12mer PNA molecule (shown in bold) coupled to a 10 amino acid peptide. [0154]
  • Growth Assay with PNA14 [0155]
  • The assay was performed as follows. Dilutions of the test culture corresponding to 10[0156] 5, 104, 103, 102 and 101 cells/ml containing PNA14 at a final concentration of 1.3, 1.4 and 1.5 μM are incubated at 37° C. for 16 hours with constant shaking. Total inhibition of growth can be seen in cultures with 104-101 cells/ml and a PNA concentration of at least 1.4 μM (Table 7).
    • Example 12 Bacterial Growth Inhibition with PNA Targeted Against the LacZ Gene
  • Peptides are truncated versions of the KFF-motif. The basic peptide sequence is KFFKFFKFFK (SEQ ID NO: 148) (PNA 1). PNA 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 all contain peptides which are truncated from the C-terminal end. PNA 84, 85, 86, 87, 88, 89, 90, 91 and 92 all contain peptides which are truncated from the N-terminal end. The PNA targeted against the LacZ-gene has been synthesized with and without an —NH[0157] 2 terminal lysine.
  • The assay was performed as follows. Dilutions of the test culture [0158] E. coli K12 corresponding to 5×105 and 5×104 cells/ml, containing truncated versions of the KFF-motif of the PNAs targeted against the LacZ gene, at final concentrations of 100, 300, 750 and 1500 nM, were incubated in M9 minimal broth with lactose as the sole carbon source (minimal media 9, Bie & Bemtsen Cph) at 37° C. for 16 hours with constant shaking.
  • Total inhibition of growth was evident in cultures with 5×10[0159] 4-105 cells/ml and a PNA concentration of at least 300 nM (see Table 8). The results show that the basic KFF motif 10-mer, as well as truncated peptides thereof (4, 5, 6, and 9-mer), may be used to enhance the inhibitory effect of PNA.
    TABLE 6
    Bacterial growth inhibition with PNA 26; E. coli K12 in
    10% Mueller-Hinton broth
    PNA conc. in wells nM
    PNA 1500 2000 2500 3000-3500
    Bacterial 1% 0.1% 0.1% 1% 0.1% 0.1% 1% 0.1% 0.1% 1% 0.1% 0.1%
    concentration 0.001% 0.0001% 0.001% 0.0001% 0.001% 0.0001% 0.001% 0.0001%
    26 − − − − − − (+) + + + + +
    − − − − + + + +
  • [0160]
    TABLE 7
    Bacterial growth inhibition with PNA 14; E. coli K12 in
    10% Mueller-Hinton broth
    PNA conc. in wells nM
    PNA 1300 1400 1500
    Bacterial 1% 0.1% 0.1% 0.001% 1% 0.1% 0.1% 0.001% 1% 0.1% 0.1%
    concentration 0.0001% 0.0001% 0.001% 0.0001%
    14 − − − − (+) + + + + + + +
    − + +
  • [0161]
    TABLE 8
    PNA conc. in well (nM)
    100 300 750 1500
    No of bacteria/ml
    PNA Peptide Lysine 5 × 105 5 × 104 5 × 105 5 × 104 5 × 105 5 × 104 5 × 105 5 × 104
    1 10-mer  + − − Nd − − (+) − Nd
    2 9-mer + − − Nd − − − − Nd
    84 9-mer − − − Nd − − + − Nd
    3 8-mer + − − Nd − − − − Nd
    85 8-mer − − − Nd − − − − Nd
    4 7-mer + − − Nd − − − − Nd
    86 7-mer − − − Nd − − − − Nd
    5 6-mer + − − Nd − − − − Nd
    87 6-mer − − − Nd + − + − Nd
    6 5-mer + − − Nd − − (+) − Nd
    88 5-mer − − − Nd − − − − Nd
    7 4-mer + − − Nd − − (+) − Nd
    89 4-mer − − − Nd − − − − Nd
    8 3-mer + − − Nd − − − − Nd
    90 3-mer − − − Nd − − − − Nd
    9 2-mer + − − Nd − − − − Nd
    91 2-mer − − − Nd − − − − Nd
    10 1-mer + − − Nd − − − − Nd
    92 1-mer − − − Nd − − − − Nd
    11 0-mer + − Nd − − − − Nd
    • Example 13 Bacterial Growth Inhibition with PNA Targeted Against the infA Gene of E. coli (Sequence as PNA 130)
  • PNA 130 and PNAs 218-226, targeted against the infA-gene, were synthesized with peptides which were truncated versions of the KFF-motif. [0162]
  • Growth Assay with PNA130 [0163]
  • The assay was performed as follows. Dilutions of the test culture [0164] E. Coli K12, corresponding to 2×104 and 4×104cells/ml, containing truncated versions of the KFF-motif in PNAs targeted against the infa-gene, at final concentrations of 200, 400, 600 800 and 1000 nM, were incubated in 10% Mueller-Hinton broth at 37° C. for 16 hours with constant shaking.
  • Total inhibition of growth was evident in cultures with 4×10[0165] 4-2×104 cells/ml and a PNA concentration of at least 600 nM (Table 9). The results reveal that the basic KFF motif 10-mer, as well as truncated peptides thereof (6 and 9-mer), may be used to enhance the inhibitory effect of PNA.
    TABLE 9
    PNA conc. in wells (nM)
    200 400 600 800 1000
    No of bacteria/ml
    PNA Peptide 4 × 104 2 × 104 4 × 104 2 × 104 4 × 104 2 × 104 4 × 104 2 × 104 4 × 104 2 × 104
    218 1-mér − − − − − − − − − −
    219 2-mér − − − − − − − − − −
    220 3-mér − − − − − − − − − −
    221 4-mér − − − − − − − − − −
    222 5-mér − − − − − − − − − −
    223 6-mér − − − − − − (+) (+) (+) (+)
    224 7-mér − − − − − − − − − −
    225 8-mér − − − − − − − − − −
    226 9-mér − − − − − + (+) + (+) +
    130 10-mér  − − − − (+) + + + + +
    • Example 14 Bacterial Growth Inhibition with PNA Targeted Against the α-Sarcine Loop of ribosomal RNA
  • PNAs 140-146, targeted against the α-sarcine loop of ribosomal RNA, were synthesized with peptides which were truncated versions of the KFF-motif. [0166]
  • Growth Assay [0167]
  • The assay was performed as follows. Dilutions of the test culture [0168] E. coli K12, corresponding to 2×104 and 4×104 cells/ml, containing truncated versions of the KFF-motif in PNAs targeted against the a-sarcine loop of ribosomal RNA, at final concentrations of 200, 400, 600, 800 and 1000 nM, were incubated in 10% Mueller-Hinton broth at 37° C. for 16 hours with constant shaking.
  • Total inhibition of growth was evident in cultures with 5×10[0169] 5-5×104 cells/ml and a PNA concentration of at least 200 nM (Table 10). The results demonstrate that the basic KFF motif 10-mer, as well as all truncated peptides thereof comprising at least 3 amino acids, may be used to enhance the inhibitory effect of PNA.
    TABLE 10
    PNA conc. in wells (nM)
    200 400 600 800 1000
    Bacteria/ml
    PNA Peptide 5 × 105 5 × 104 5 × 105 5 × 104 5 × 105 5 × 104 5 × 105 5 × 104 5 × 105 5 × 104
    140 3-mér − − − − − (+) (+) (+) (+)
    141 4-mér (+) + + + + + + + + +
    142 5-mér − (+) (+) + (+) + + + + +
    143 6-mér + + + + + + + + + +
    144 7-mér − (+) + + + + + + + +
    145 8-mér (+) (+) (+) + + + + + + +
    146 9-mér − (+) + + + + + + nd nd
    • Example 15 Bacterial Growth Inhibition with PNA Against the FtsZ Gene of E. coli K12
  • Growth Assay with PNA170-179 and 109 [0170]
  • The assay was performed as follows. Dilutions of the test culture [0171] E. coli K12, 20 corresponding to 700 and 350 cells/ml, containing variations of amphipathic 10, 11 and 12-mer structures with smcc-linker in PNAs targeted against the FtsZ-gene, at final concentrations of 200, 300, 400, 500, 600, 800 and 1000 nM, were incubated in 100% Mueller-Hinton broth at 37° C. for 16 hours with constant shaking.
  • Total inhibition of growth was evident in cultures with 350-700 cells/ml and a PNA concentration of at least 300 nM (Table 11). When comparing PNA109 with PNA 179, the smcc linker appears to add some advantages to the molecule. Further, sequence 174 shows promising results. [0172]
    TABLE 11
    Conc. PNA construct
    200 nM 300 nM 400 nM 500 nM 600 nM 800 nM 1000 nM
    No of bacteria/ml
    PNA Peptide 700 350 700 350 700 350 700 350 700 350 700 350 700 350
    170 12-mér − − − − − − − − − − − − − −
    171 12-mér − − − − − − − − − − + + + (+)
    172 12-mér − − − − − − − − − − − − − −
    173 12-mér − − − − − − − − − − − − − −
    174 12-mér − − − + − + + + + + + + + +
    175 12-mér − − − − − − − − − − − − − −
    176 12-mér − − − − − − − − − − (+) (+) + +
    177 12-mér − − − − − − − − − − − − − −
    178 12-mér − − − − − − − − − − − − − −
    179 11-mér − − + + (+) (+) + + + + + + + +
    109 10-mér − − − − − − − − − − (+) (+) (+) (+)
    • Example 16 Bacterial Growth Inhibition by PNAs, Which Contain Various Linkers and Peptides, Targeted Against the Gene Encoding IF-1 of E. coli
  • For the 7 PNA's in this set-up, the sequence of the nucleobases is the same as the sequence in PNA 130, but the linking groups and the peptides vary. [0173]
    TABLE 12
    PNA Linker Peptide
    PNA228 ahex-ado G-KLAKALKKLL (SEQ ID NO: 149)
    PNA229 ado-ado G-KLAKALKKLL (SEQ ID NO: 150)
    PNA230 ado-ado KFFKFFKFF (SEQ ID NO: 151)
    PNA231 ahex-ado KFFKFFKFF (SEQ ID NO: 152)
    PNA232 smcc-ado H-C-KFFKFFKFFK-NH2 (SEQ ID NO: 153)
    PNA233 smcc-ado H-CG-KLAKALKKLL-NH2 (SEQ ID NO: 154)
    PNA234 smcc-ado H-C-FFKFFK-NH2 (SEQ ID NO: 155)
  • The experimental set-up corresponds to the set-up as described in Example 15. As is evident from Table 13 and 14, the smcc-ado linker is the superior linker, demonstrating total inhibition of growth in cultures with 1.6×10[0174] 3-8×102 cells/ml and a PNA concentration of at least 600 nM.
    TABLE 13
    PNA conc. in wells (nM)
    200 400 600 800 1000
    No of bacteria/ml based on counting of colonies on agar plates
    PNA 1590 795 159 1590 795 159 1590 795 159 1590 795 159 1590 795 159
    228 − − − − − − − − − − − − − − −
    229 − − − − − − − − − − − − − − −
    230 − − − − − − − − − − − − − − −
    231 − − − − − − − − − − − − − − −
    232 − − − (+) (+) (+) + + + + + + + + +
    233 − − − (+) (+) (+) + + + + + + + + +
    234 − − − − − − − − − − − − − − −
  • [0175]
    TABLE 14
    PNA conc. in wells (nM)
    200 400 600 800 1000
    No of bacteria/ml based on counting of colonies on agar plates
    PNA 105 104 103 105 104 103 105 104 103 105 104 103 105 104 103
    228 − − − − − − − − − − − (+) − (+) +
    229 − − − − − − − − − − (+) (+) − (+) +
    230 − − − (+) (+) + + + + + + + + + +
    231 − − − − (+) (+) (+) + + + + + + + +
    232
    nd
    233
    nd
    234
    nd
    • Example 17 Bacterial Growth Inhibition with 9 mer Peptide
  • To test the effect of a Peptide without a PNA, peptide no. 2339, H-KFFKFFKFF-OH (SEQ ID NO: 1), was added to [0176] E. coli K12 in 10% and 100% medium (Mueller-Hinton broth).
  • Growth Assay of Peptide no. 2339 [0177]
  • The assay was performed as follows. Dilutions of the test culture corresponding to 10[0178] 5, 104, and 103 cells/ml containing peptide no. 2339 at a final concentration of 100 to 20,000 nM, were incubated at 37° C. for 16 hours with constant shaking. Total inhibition of growth was evident in cultures with 7.9×103 cells/ml and a peptide concentration of at least 20,000 nM, and minimal signs of growth inhibition were detected at concentrations from 5,000 nM (10% medium: Table 15; 100% medium: Table 16). The peptide was thus active alone, but only at very high concentrations which were above the range used for PNA growth assays.
    TABLE 15
    Peptide conc. in wells (nM)
    100 300 500 700
    No. of bacteria/ml based on counting of colonies on agar plates
    Pep-
    tide 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103
    2339 − − − − − − − − − − − −
    Peptide conc. in wells (nM)
    900 1100 1300 1500
    No. of bacteria/ml based on counting of colonies on agar plates
    Pep-
    tide 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103
    2339 − − − − − − − − − − − −
    Peptide conc. in wells (nM)
    2500 5000 10000 15000
    No. of bacterial/ml based on counting of colonies on agar plates
    Pep-
    tide 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103 4.0 × 104 7.9 × 103 4.0 × 103
    2339 − − − ((+)) ((+)) ((+)) ((+)) ((+)) ((+)) ((+)) ((+)) ((+))
    Peptide conc. in wells (nM)
    20000
    No. of bacterial/ml based on
    counting of colonies on agar plates
    Peptide 4.0 × 104 7.9 × 103 4.0 × 103
    2339 ((+)) + +
  • [0179]
    TABLE 16
    Peptide conc. in wells (nM)
    100 300 500 700 900 1100
    No. of bacteria/ml based on counting of colonies on agar plates
    Peptide 1600 160 16 1600 160 16 1600 160 16 1600 160 16 1600 160 16 1600 160 16
    2339 − − − − − − − − − − − − − − − − − −
    Peptide conc. in wells (nM)
    1300 1500 2500 5000 10000 15000
    No. of bacteria/ml based on counting of colonies on agar plates
    Peptide 1600 160 16 1600 160 16 1600 160 16 1600 160 16 1600 160 16 1600 160 16
    2339 − − − − − − − − − − − − − − − − − −
    Peptide
    conc. in wells
    (nM)
    20000
    No. of bacteria/ml
    based on counting
    of colonies
    on agar plates
    Peptide 1600 160 16
    2339 − − (+)
    • Example 18 Bacterial Growth Inhibition with 9 mer Peptide and Non-Sense PNA
  • Growth Assay of the Peptide No. 2339 Together with Nonsense PNA 136 [0180]
  • The assay was performed as follows. Dilutions of the test culture corresponding to 10[0181] 5, 104 and 103 cells/ml, containing PNA 136 alone or PNA 136 and peptide No. 2339 in equal amounts, at a final concentration of 400 to 1000 nM, were incubated at 37° C. for 16 hours with constant shaking. No growth inhibition was detected at any of the concentrations (Table 17). The nonsense PNA was thus not active in the chosen range.
    TABLE 17
    PNA/Peptide conc. in wells (nM)
    400 500 600 700
    Dilution factor for stock solution of bacteria with OD600 = 0.1
    PNA Peptide F102 F103 F104 F102 F103 F104 F102 F103 F104 F102 F103 F104
    2339 − − − − − − − − − − − −
    136 − − − − − − − − − − − −
    PNA/Peptide conc. in wells (nM)
    800 900 1000
    Dilution factor for stock solution of
    bacteria with OD600 = 0.1
    PNA Peptide F102 F103 F104 F102 F103 F104 F102 F103 F104
    2339 − − − − − − − − −
    136 − − − − − − − − −
    • Example 19 Bacterial Growth Inhibition with PNA (Without Peptide) Targeted Against the Gene Encoding FtsZ of E. coli and a Peptide
  • [0182] E. coli K12 was grown in 100% Mueller-Hinton broth. PNA 249 is identical to PNA 109, without the peptide but still with the ado-linker. The Peptide of PNA 250 has the sequence: H-CG-KLAKALKKLL-NH2 (SEQ ID NO: 156). The peptide is also used for PNA 174. In the wells with both PNA and peptide there is equal amount PNA and peptide. As can be seen in Table 18, neither 249 nor 250 alone nor 249 and 250 together show any useful effect in the low concentration end. Only the peptide alone in concentrations above 2500 nM may show growth inhibition effect.
    TABLE 18
    PNA conc. in wells (nM)
    250 500 750 1000 1500 2000 2500 5000
    No of bacteria/ml based on counting of colonies on agar plates
    PNA Peptide 170 17 8 170 17 8 170 17 8 170 17 8 170 17 8 170 17 8 170 17 8 170 17 8
    249 − − − − − − − − − − − − − − − − − − − − − nd nd nd
    250 nd nd nd − − − nd nd nd − − − − − − nd nd nd − − − (+) (+) +
    PNA conc. in wells (nM)
    10000 20000 500 + 500 1000 + 1000 1500 + 1500 2500 + 2500
    No of bacteria/ml based on counting of colonies on agar plates
    PNA Peptide 170 17 8 170 17 8 170 17 8 170 17 8 170 17 8 170 17 8
    nd nd nd nd nd nd − − − − − − − − − − − −
    249 250 + + + + + +
    • Example 20 Bacterial Growth Inhibition with PNA Against the Gene Encoding IF-1 of E. coli
  • [0183] E. coli K12 was grown in 10% Mueller-Hinton broth. Peptides are versions of the KFF-motif placed C- or N-terminal to the PNA. From Table 19 it can be seen that both orientation of the Peptide work. However, for specific combinations of PNA and Peptide, one of the orientations may be preferred.
    TABLE 19
    PNA conc. in wells (nM)
    200 400 600 800 1000
    No of bacteria/ml based on counting of colonies on agar plates
    5.2 × 2.6 × 5.2 × 5.2 × 2.6 × 5.2 × 5.2 × 2.6 × 5.2 × 5.2 × 2.6 × 5.2 × 5.2 × 2.6 × 5.2 ×
    PNA Peptide Place 104 104 103 104 104 103 104 104 103 104 104 103 104 104 103
    130 10-mér N − − − − (+) (+) (+) + + + + + + + +
    214 10-mér C − − − (+) + + + + + + + + + + +
    215  9-mér C − − − (+) + + (+) + + + + + + + +
    216  6-mér C − − − − − − − − − − − − − (+) (+)
    223  6-mér N − − − − − − − − − − − − − − −
    226  9-mér N − − − − − − − (+) + (+) + + + + 52
    • Example 21 Inhibition of Bacterial Growth by PNA-Peptide Specific for the Ribosomal α-sarine Loop
  • To demonstrate that the present invention may be used for the treatment of many micro-organisms, a selection of Gram-negative and Gram-positive bacteria were treated under the same assay conditions as used in example 14. The modified PNA molecule used was PNA 146. [0184]
    Inhibition of growth
    Gram-negative organisms
    Escherichia coli +
    Klebsiella pneumonia +
    Pseudomonas aeruginosa +
    Salmonella typhimurium +
    Gram-positive organisms
    Staphylococcus aureus +
    Enterococcus faecium +
    Micrococcos luteus +
  • Growth of the bacterial isolates was inhibited. Growth inhibition of different Gram-negative and Gram-positive organisms has thus been demonstrated under the same assay conditions as were used for the testing of [0185] E. coli K.12.
    • Example 22 Preparation of Peptide-PNA-Chimeras
  • The following peptide-PNA-chimera was prepared as described in Example 1: H[0186] 2N-SILAPLGTTLVKKVATTLKKIFSKWKC-smcc-Ado-TTCTAACATTTA-NH2 (SEQ ID NO: 159).
    • Example 23 Gene Target Selection and Bacterial Growth Inhibition with PNA
  • Gene Target Selection in [0187] E. faecalis/E. faecium
  • The annotated [0188] E. faecium genome is, along with 250 other genomes, commercially available from Integrated Genomics, Chicago. Single annotated genes from both organisms are also available in Genbank.
  • In vitro Experiments [0189]
  • The ability of PNA conjugates to inhibit bacterial growth is measured by the use of a microdilution broth method using 100% Mueller-Hinton broth, according to NCCLS Guidelines. A logphase culture of [0190] E. faecium is diluted with fresh, prewarmed medium and adjusted to a defined OD (here: Optical Density at 600 nm) to yield a final concentration of 1×104 bacteria/ml medium in each well, which contain 195 μl of bacterial culture. PNA is added to the bacterial culture to yield final concentrations ranging from 450 nM to 1500 nM. Trays (e.g. Costar #3474) are incubated at 35° C. by shaking in a robot analyzer (96 well microtiter format), PowerWavex, software KC4, Kebo.Lab, Copenhagen, for 16 hours and optical densities are measured at 600 nm during the incubation in order to record growth curves. All cultures are tested for the presence of contaminants.
  • MIC and MBC [0191]
  • Experiments were performed to evaluate the relationship between MIC's and MBC's (Minimal Bactericidal Concentration) of the PNA. The studies were performed using 3 strains of [0192] Enterococcus faecium obtained from American Type Culture Collection (ATCC). These strains served as initial indicators of possible interference from known in vivo-selected vancomycin resistance mechanisms. The table below summarizes the characteristics of the strains.
  • [0193] E. facium Strain: Description
  • 8803: susceptible to vancomycin, ciprofloxacin, gentamycin, rifampin, teicoplanin [0194]
  • ATCC 51550: multidrugresistant (ampicillin, ciprofloxacin, gentamycin, rifampin, teicoplanin, vancomycin [0195]
  • ATCC 700221: resistant to vancomycin [0196]
  • The experimental design is as follows. MIC's were detected as previously described. Trays were incubated at 35° C. for an additional 24 hours in order to analyze regrowth of inhibited bacteria (MBC's). The PNA conjugate from Example 22 was used as were bacterial strains 8803, 51550, and 700221. The PNA concentration in wells was 400, 800 and 1600 nM. [0197]
  • The Minimal Inhibitory Concentrations (MIC's) of the PNA conjugate were as follows: [0198]
    MIC MBC
    E. facium Strain μg/ml-(nM) (μg/ml)-nM
    8803 ≦400 ≦400
    ATCC 51550 ≦400 ≦400
    ATCC 700221 ≦400 ≦400
    Peptide control >5000 >5000
    The peptide conjugate
    of Example 22
    • Example 24 Preparation of Peptide-PNA-Chimeras
  • The following peptide-PNA-chimera was prepared as described in Example 1: H[0199] 2N-KKFKVKFVVKKC-smcc-Ado-ACTTTGTCGCCC-NH2 (SEQ ID NO: 160).
    • Example 25 Gene Target Selection and Bacterial Growth Inhibition with PNA
  • The selection of potential gene targets and testing of resultant PNA constructs were performed with [0200] Staphylococcus aureus NCTC 8325, which was obtained from Prof. J. Iandolo, University of Oklahoma Health Sciences Center, Department of Microbiology and Immunology. The genome of S.aureus NCTC 8325 is currently being sequenced at the S. aureus Genome Sequencing Project at the University of Oklahoma's Advanced Center for Genome Technology (OU-ACGT). The genome is 2.80 Mb, and 2,581,379 bp have been sequenced. Annotated gene sequences are available from Genbank for a number of putative targets.
  • Target Selection Approach [0201]
  • The basic approach used was similar to that used in the previous example. Potential target genes were retrieved from the unfinished genome sequences of [0202] S. aureus at the OU-ACGT, as well as Genbank. The presence of homologous genes and target sequences in bacterial genomes were tested using the BLAST 2.0 programs at the NCBI (National Center for Biotechnology Information) www BLAST server. The antibacterial PNA conjugate prepared in Example 24 was used in the following experiments.
  • In vitro Experiments [0203]
  • The ability of PNA to inhibit bacterial growth is measured by the use of a microdilution broth method using 100% Mueller-Hinton broth, according to NCCLS Guidelines. A logphase culture of [0204] S aureus is diluted with fresh, pre-warmed medium and adjusted to a defined OD (here: Optical Density at 600 nm) in order to yield a final concentration of 1×104 bacteria/ml medium in each well, which contains 195 μl of bacterial culture. PNA is added to the wells in order to yield final concentrations of 450 nM to 1500 nM. Trays (e.g. Costar #3474) are incubated at 35° C. by shaking in a robot analyzer (96 well microtiter format), PowerWavex, software KC4. Kebo.Lab, Copenhagen, for 16 hours and optical densities are measured at 600 nm during the incubation in order to record growth curves. All cultures are tested for the presence of contaminants.
  • MIC and MBC: [0205]
  • Experiments were also performed to evaluate the relationship between MIC's (Minimal Inhibitory Concentration) and MBC's (Minimal Bactericidal Concentration) of the PNA's. The experiments were performed using the reference strain [0206] Staphylococcus aureus NCTC 8325 obtained from Prof. J. Iandolo, University of Oklahoma Health Sciences Center, Department of Microbiology and Immunology. Two vancomycin resistant isolates of S.aureus obtained from American Type Culture Collection were also used. These strains served as initial indicators of possible interference from known in vivo-selected vancomycin resistance mechanisms. The table below summarizes the characteristics of the strains.
    Vancomycin
    S.aureus Strain Description MIC (μg/ml)
    8325 susceptible to methicillin, vancomycin <0.5
    ATCC 700698 intermediate vancomycin resistance 2
    Resistant to methicillin
    ATCC 700698R highly vancomycinresistant subclone of 11
    ATCC 700698
  • The experimental design is as follows. MIC's were detected as described above. Trays were incubated at 35° C. for an additional 24 hours in order to analyze regrowth of inhibited bacteria (MBC's). The PNA from Example 24 was used as were bacterial strains 8325, 700698, and 700698R. PNA concentrations in the wells were 400, 800 and 1600 nM. The Minimal Inhibitory Concentrations (MIC) were as follows: [0207]
    MIC MBC
    S.aureus Strain μg/ml (nM) (μg/ml) nM
    8325 800/1600   1600
    ATCC 700698 800/1600   1600
    ATCC 700698R 800/1600 ≧1600
  • Peptide control [0208]
    The peptide conjugate >5000 >5000
    of Example 24
    • Example 26 Measurement of Antibacterial Effect in vivo
  • A compound of the invention was tested for antibacterial effect in vivo according to the test described by N. Frimodt-Møller. Untreated animals developed fulminant clinical signs of infection. At all time points the compound of the invention suppressed the [0209] E. coli cfu/ml as compared to non-treated controls and was as efficient as the two positive controls.
  • All patents, patent publications, and literature references cited in this specification are hereby incorporated by reference in their entirety. [0210]
  • 0
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    <210> SEQ ID NO 18
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    <213> ORGANISM: Artificial Sequence
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
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    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
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    <221> NAME/KEY: misc_feature
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    <223> OTHER INFORMATION: Xaa is lysine-ado
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    <221> NAME/KEY: misc_feature
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    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
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    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
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    <221> NAME/KEY: misc_feature
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    <221> NAME/KEY: misc_feature
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    <221> NAME/KEY: misc_feature
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    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 19
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    <213> ORGANISM: Artificial Sequence
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    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
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    <221> NAME/KEY: misc_feature
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
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    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
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    <221> NAME/KEY: misc_feature
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
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    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
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    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
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    <211> LENGTH: 33
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
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    <400> SEQUENCE: 20
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    <210> SEQ ID NO 21
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
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    <221> NAME/KEY: misc_feature
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
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    <221> NAME/KEY: misc_feature
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    <221> NAME/KEY: misc_feature
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(19)
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is leucine
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    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 22
    <211> LENGTH: 25
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
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    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (25)..(25)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 22
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20 25
    <210> SEQ ID NO 23
    <211> LENGTH: 16
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 23
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    <210> SEQ ID NO 24
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <400> SEQUENCE: 24
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 25
    <211> LENGTH: 21
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(20)
    <223> OTHER INFORMATION: Xaa N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa N-(2-Boc-aminoethyl)-N-(N4-(be
    nzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 25
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 26
    <211> LENGTH: 20
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <400> SEQUENCE: 26
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 27
    <211> LENGTH: 19
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)gl
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 27
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa
    <210> SEQ ID NO 28
    <211> LENGTH: 18
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <400> SEQUENCE: 28
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa
    <210> SEQ ID NO 29
    <211> LENGTH: 17
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <400> SEQUENCE: 29
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa
    <210> SEQ ID NO 30
    <211> LENGTH: 17
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycinee
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <400> SEQUENCE: 30
    Xaa Xaa Xaa Xaa Xaa Cys Ala Thr Ala Gly Cys Thr Gly Thr Thr Thr
    1 5 10 15
    Cys
    <210> SEQ ID NO 31
    <211> LENGTH: 15
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine -ado
    <400> SEQUENCE: 31
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    <210> SEQ ID NO 32
    <211> LENGTH: 14
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-(benzy
    loxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <400> SEQUENCE: 32
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10
    <210> SEQ ID NO 33
    <211> LENGTH: 13
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 33
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10
    <210> SEQ ID NO 34
    <211> LENGTH: 12
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 34
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10
    <210> SEQ ID NO 35
    <211> LENGTH: 21
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 35
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 36
    <211> LENGTH: 20
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <400> SEQUENCE: 36
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 37
    <211> LENGTH: 19
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 37
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa
    <210> SEQ ID NO 38
    <211> LENGTH: 17
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 38
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa
    <210> SEQ ID NO 39
    <211> LENGTH: 17
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <400> SEQUENCE: 39
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa
    <210> SEQ ID NO 40
    <211> LENGTH: 16
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 40
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    <210> SEQ ID NO 41
    <211> LENGTH: 15
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 41
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    <210> SEQ ID NO 42
    <211> LENGTH: 14
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 42
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10
    <210> SEQ ID NO 43
    <211> LENGTH: 13
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 43
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10
    <210> SEQ ID NO 44
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <400> SEQUENCE: 44
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 45
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-y
    l-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <400> SEQUENCE: 45
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 46
    <211> LENGTH: 18
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <400> SEQUENCE: 46
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa
    <210> SEQ ID NO 47
    <211> LENGTH: 18
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 47
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa
    <210> SEQ ID NO 48
    <211> LENGTH: 20
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 48
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 49
    <211> LENGTH: 21
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-ado-ado e
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 49
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 50
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 50
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 51
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2
    -(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (N-2-(benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-do-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 51
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 52
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine-ado-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N-2-
    (benzyloxycarbonyl)isocytosine-5-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 52
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 53
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 53
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 54
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is arginine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is arginine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is arginine
    <400> SEQUENCE: 54
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 55
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(8)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 55
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 56
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is arginine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is arginine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(8)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is arginine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 56
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 57
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 57
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 58
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is tryptophan
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(7)
    <223> OTHER INFORMATION: Xaa is tryptophan
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is tryptophan
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is arginine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is proline
    <400> SEQUENCE: 58
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 59
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(8)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <400> SEQUENCE: 59
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 60
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(6)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(10)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 60
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 61
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is lN-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <400> SEQUENCE: 61
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 62
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 62
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 63
    <211> LENGTH: 13
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 63
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10
    <210> SEQ ID NO 64
    <211> LENGTH: 14
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 64
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10
    <210> SEQ ID NO 65
    <211> LENGTH: 15
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 65
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    <210> SEQ ID NO 66
    <211> LENGTH: 16
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 66
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    <210> SEQ ID NO 67
    <211> LENGTH: 17
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 67
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa
    <210> SEQ ID NO 68
    <211> LENGTH: 18
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 68
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa
    <210> SEQ ID NO 69
    <211> LENGTH: 19
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 69
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa
    <210> SEQ ID NO 70
    <211> LENGTH: 20
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(5)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 70
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 71
    <211> LENGTH: 21
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado
    <400> SEQUENCE: 71
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 72
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is leucine
    <400> SEQUENCE: 72
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 73
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado-ado
    <400> SEQUENCE: 73
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 74
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ahex-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 74
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 75
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 75
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 76
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is leucine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 76
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 77
    <211> LENGTH: 19
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <400> SEQUENCE: 77
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa
    <210> SEQ ID NO 78
    <211> LENGTH: 12
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(6)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(8)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is
    <400> SEQUENCE: 78
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10
    <210> SEQ ID NO 79
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 79
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 80
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is lcysteine-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 80
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 81
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-achc-beta.ala
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 81
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 82
    <211> LENGTH: 21
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-achc-beta.ala
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 82
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 83
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-lcsmcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 83
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 84
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-mbs-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 84
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 85
    <211> LENGTH: 25
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-emcs-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is emcs-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <400> SEQUENCE: 85
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Thr Cys
    1 5 10 15
    Ala Ala Ala Cys Ala Thr Ala Gly Thr
    20 25
    <210> SEQ ID NO 86
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smph-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <400> SEQUENCE: 86
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 87
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-amas-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 87
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 88
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-smpbeta-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 88
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 89
    <211> LENGTH: 25
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-lcsmcc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (25)..(25)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 89
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20 25
    <210> SEQ ID NO 90
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-lcsmcc-beta.ala
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <400> SEQUENCE: 90
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 91
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-lcsmcc-beta.cypr
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)gl
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 91
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 92
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-lcsmcc-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <400> SEQUENCE: 92
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 93
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is valine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is cysteine-lcsmcc-adc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 93
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 94
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 94
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 95
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 95
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 96
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 96
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 97
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 97
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 98
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 98
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 99
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado-achc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 99
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 100
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 100
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 101
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 101
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 102
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 102
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 103
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <400> SEQUENCE: 103
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 104
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <400> SEQUENCE: 104
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 105
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine-achc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <400> SEQUENCE: 105
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 106
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 106
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 107
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 107
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 108
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(2)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is -(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <400> SEQUENCE: 108
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 109
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 109
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 110
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 110
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 111
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline-achc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 111
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 112
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-aha-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 112
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 113
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is -(2-Boc-aminoethyl)-N-(N6-(
    benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 113
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 114
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 114
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 115
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-aha-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(23)
    <223> OTHER INFORMATION: Xaa is
    <400> SEQUENCE: 115
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 116
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine-aha-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-aha-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 116
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 117
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-aha-achc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <400> SEQUENCE: 117
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 118
    <211> LENGTH: 21
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-beta.alanine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 118
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 119
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycin
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 119
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 120
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 120
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 121
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-beta.alanine-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 121
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 122
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-beta.alanine-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <400> SEQUENCE: 122
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 123
    <211> LENGTH: 21
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-beta.alanine-achc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 123
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 124
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is Proline-p
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 124
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 125
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 125
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 126
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(12)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 126
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 127
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 127
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 128
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 128
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 129
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 129
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 130
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-phenylglycine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 130
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 131
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-phenylglycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 131
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 132
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-phg
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is -(2-Boc-aminoethyl)-N-(N4-(
    benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is
    <400> SEQUENCE: 132
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 133
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-phenylglycine-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 133
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 134
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-phg-beta.alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 134
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 135
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-phenylglycine-achc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is
    <400> SEQUENCE: 135
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 136
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-achc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <400> SEQUENCE: 136
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 137
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycinelycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-achc
    <400> SEQUENCE: 137
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 138
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-achc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is proline
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 138
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 139
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-achc-aha
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 139
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 140
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-achc-b-alanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 140
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 141
    <211> LENGTH: 22
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-achc-achc
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <400> SEQUENCE: 141
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 142
    <211> LENGTH: 30
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <400> SEQUENCE: 142
    Ala Ala Thr Gly Gly Gly Ala Ala Ala Thr Thr Thr Cys Cys Ala Gly
    1 5 10 15
    Thr Gly Ala Ala Gly Thr Thr Cys Gly Thr Ala Ala Ala Gly
    20 25 30
    <210> SEQ ID NO 143
    <211> LENGTH: 30
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <400> SEQUENCE: 143
    Cys Thr Thr Thr Ala Cys Gly Ala Ala Cys Thr Thr Cys Ala Cys Thr
    1 5 10 15
    Gly Gly Ala Ala Ala Thr Thr Thr Cys Cys Cys Ala Thr Thr
    20 25 30
    <210> SEQ ID NO 144
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <400> SEQUENCE: 144
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 145
    <211> LENGTH: 33
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <400> SEQUENCE: 145
    Gly Ala Gly Thr Ala Gly Ala Ala Ala Ala Cys Gly Cys Ala Gly Cys
    1 5 10 15
    Gly Gly Ala Thr Gly Ala Ala Ala Cys Thr Ala Cys Ala Gly Ala Ala
    20 25 30
    Cys
    <210> SEQ ID NO 146
    <211> LENGTH: 33
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <400> SEQUENCE: 146
    Gly Thr Thr Cys Thr Gly Thr Ala Gly Thr Thr Thr Cys Ala Thr Cys
    1 5 10 15
    Cys Gly Cys Thr Gly Cys Gly Thr Thr Thr Thr Cys Thr Ala Cys Thr
    20 25 30
    Cys
    <210> SEQ ID NO 147
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(3)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(6)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is lysine-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(16)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (17)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is lysine
    <400> SEQUENCE: 147
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20
    <210> SEQ ID NO 148
    <211> LENGTH: 10
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <400> SEQUENCE: 148
    Lys Phe Phe Lys Phe Phe Lys Phe Phe Lys
    1 5 10
    <210> SEQ ID NO 149
    <211> LENGTH: 11
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is leucine-ahex-ado
    <400> SEQUENCE: 149
    Gly Lys Leu Ala Lys Ala Leu Lys Lys Leu Xaa
    1 5 10
    <210> SEQ ID NO 150
    <211> LENGTH: 11
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is leucine-ado-ado
    <400> SEQUENCE: 150
    Gly Lys Leu Ala Lys Ala Leu Lys Lys Leu Xaa
    1 5 10
    <210> SEQ ID NO 151
    <211> LENGTH: 9
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ado-ado
    <400> SEQUENCE: 151
    Lys Phe Phe Lys Phe Phe Lys Phe Xaa
    1 5
    <210> SEQ ID NO 152
    <211> LENGTH: 9
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (9)..(9)
    <223> OTHER INFORMATION: Xaa is phenylalanine-ahex-ado
    <400> SEQUENCE: 152
    Lys Phe Phe Lys Phe Phe Lys Phe Xaa
    1 5
    <210> SEQ ID NO 153
    <211> LENGTH: 11
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is lysine-smcc-ado
    <400> SEQUENCE: 153
    Cys Lys Phe Phe Lys Phe Phe Lys Phe Phe Xaa
    1 5 10
    <210> SEQ ID NO 154
    <211> LENGTH: 12
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is leucine-smcc-ado
    <400> SEQUENCE: 154
    Cys Gly Lys Leu Ala Lys Ala Leu Lys Lys Leu Xaa
    1 5 10
    <210> SEQ ID NO 155
    <211> LENGTH: 7
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is lysine-smcc-ado
    <400> SEQUENCE: 155
    Cys Phe Phe Lys Phe Phe Xaa
    1 5
    <210> SEQ ID NO 156
    <211> LENGTH: 12
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <400> SEQUENCE: 156
    Cys Gly Lys Leu Ala Lys Ala Leu Lys Lys Leu Leu
    1 5 10
    SEQ ID NO 157
    LENGTH: 7
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <400> SEQUENCE: 157
    Lys Phe Phe Lys Phe Phe Lys
    1 5
    <210> SEQ ID NO 158
    <211> LENGTH: 23
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <400> SEQUENCE: 158
    Gly Ile Gly Lys Phe Leu His Ala Ala Lys Lys Phe Ala Lys Ala Phe
    1 5 10 15
    Val Ala Glu Ile Met Asn Ser
    20
    <210> SEQ ID NO 159
    <211> LENGTH: 39
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(1)
    <223> OTHER INFORMATION: Xaa is Ser
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (2)..(2)
    <223> OTHER INFORMATION: Xaa is Ile
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is Leu
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is Ala
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is Pro
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is Leu
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is Gly
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is Thr
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(10)
    <223> OTHER INFORMATION: Xaa is Leu
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (11)..(11)
    <223> OTHER INFORMATION: Xaa is Val
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(13)
    <223> OTHER INFORMATION: Xaa is Lys
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is Val
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(15)
    <223> OTHER INFORMATION: Xaa is Ala
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (16)..(17)
    <223> OTHER INFORMATION: Xaa is Thr
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is Leu
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(20)
    <223> OTHER INFORMATION: Xaa is Lys
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is Ile
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(22)
    <223> OTHER INFORMATION: Xaa is Phe
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (23)..(23)
    <223> OTHER INFORMATION: Xaa is Ser
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (24)..(24)
    <223> OTHER INFORMATION: Xaa is Lys
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (25)..(25)
    <223> OTHER INFORMATION: Xaa is Trp
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (26)..(26)
    <223> OTHER INFORMATION: Xaa is Trp
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (27)..(27)
    <223> OTHER INFORMATION: Xaa is Cys-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (28)..(29)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (30)..(30)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (31)..(31)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (32)..(33)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (34)..(34)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (35)..(35)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (36)..(38)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (39)..(39)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <400> SEQUENCE: 159
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20 25 30
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    35
    <210> SEQ ID NO 160
    <211> LENGTH: 24
    <212> TYPE: PRT
    <213> ORGANISM: Artificial Sequence
    <220> FEATURE:
    <223> OTHER INFORMATION: Synthetic Construct
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (1)..(2)
    <223> OTHER INFORMATION: Xaa is Lys
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (3)..(3)
    <223> OTHER INFORMATION: Xaa is Phe
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (4)..(4)
    <223> OTHER INFORMATION: Xaa is Lys
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (5)..(5)
    <223> OTHER INFORMATION: Xaa is Val
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (6)..(6)
    <223> OTHER INFORMATION: Xaa is Lys
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (7)..(7)
    <223> OTHER INFORMATION: Xaa is Phe
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (8)..(9)
    <223> OTHER INFORMATION: Xaa is Val
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (10)..(11)
    <223> OTHER INFORMATION: Xaa is Lys
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (12)..(12)
    <223> OTHER INFORMATION: Xaa is Cys-smcc-ado
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (13)..(13)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N6-
    (benzyloxycarbonyl)adenine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (14)..(14)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (15)..(17)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (18)..(18)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (19)..(19)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-
    (thymine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (20)..(20)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (21)..(21)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N2-
    (benzyloxycarbonyl)guanine-9-yl-acetyl)glycine
    <220> FEATURE:
    <221> NAME/KEY: misc_feature
    <222> LOCATION: (22)..(24)
    <223> OTHER INFORMATION: Xaa is N-(2-Boc-aminoethyl)-N-(N4-
    (benzyloxycarbonyl)cytosine-1-yl-acetyl)glycine
    <400> SEQUENCE: 160
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    1 5 10 15
    Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
    20

Claims (47)

We claim:
1. A modified oligonucleotide having formula (III):
Peptide-L-Oligon  (III)
wherein L is a linker or a bond, Peptide is any amino acid sequence, and Oligon is an oligonucleotide or analog thereof.
2. A composition comprising the modified oligonucleotide of claim 1 or a pharmaceutically acceptable salt thereof.
3. The composition of claim 2 further comprising an antibiotic.
4. The modified oligonucleotide of claim 1 wherein L comprises at least one of the following: 8-amino-3,6-dioxaoctanoic acid (ADO), succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), 6-aminohexanoic acid (AHEX), 4-aminobutyric acid, 4-aminocyclohexylcarboxylic acid, polyethylene glycol, any amino acid, or any combination thereof.
5. A modified peptide nucleic acid (PNA) molecule having formula (I):
Peptide-L-PNA  (I)
wherein L is a linker or a bond, Peptide is any amino acid sequence, and PNA is a peptide nucleic acid.
6. The modified PNA molecule of claim 5 wherein Peptide is a cationic peptide or peptide analog or a functionally similar moiety having formula (II):
C-(B-A)n-D,  (II)
wherein:
A is from 1 to 8 non-charged amino acids and/or amino acid analogs;
B is from 1 to 3 positively charged amino acids and/or amino acid analogs;
C is from 0 to 4 non-charged amino acids and/or amino acid analogs;
D is from 0 to 3 positively charged amino acids and/or amino acid analogs; and
n is 1-10;
wherein the total number of amino acids and/or amino acid analogs is from 3 to 20.
7. The modified PNA molecule of claim 5 wherein L comprises at least one of the following: 8-amino-3,6-dioxaoctanoic acid (ADO), succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), 6-aminohexanoic acid (AHEX), 4-aminobutyric acid, 4-aminocyclohexylcarboxylic acid, polyethylene glycol, any amino acid, or any combination thereof.
8. The modified PNA molecule of claim 7 wherein L comprises a combination of β.ALA or ADO and any one of SMCC, AHEX, 4-aminobutyric acid, 4-aminocyclohexylcarboxylic acid, polyethylene glycol, and any amino acid.
9. The modified PNA molecule of claim 8 wherein L is selected from the group consisting of: -achc-β.ala-, -achc-ado-, -lcsmcc-β.ala-, -mbs-β.ala-, -emcs-β.ala-, -lcsmcc-ado-, -mbs-ado-, -emcs-ado- or -smph-ado-.
10. The modified PNA molecule of claim 5 wherein A comprises from 1 to 6 non-charged amino acids and/or amino acid analogs and B comprises 1 or 2 positively charged amino acids and/or amino acid analogs.
11. The modified PNA molecule of claim 10 wherein A comprises from 1 to 4 non-charged amino acids and/or amino acid analogs.
12. The modified PNA molecule of claim 5 wherein the positively charged amino acids and amino acid analogs are selected from the group consisting of lysine, arginine, diamino butyric acid (DAB) and ornithine.
13. The modified PNA molecule of claim 5 wherein the non-charged amino acids and amino acid analogs are selected from the group consisting of Ala, Val, Leu, Ile, Pro, Phe, Trp, Met, Gly, Ser, Thr, Cys, Tyr, Asn, Gln and the non-naturally occurring amino acids 2-aminobutyric acid, β-cyclohexylalanine, 4-chlorophenylalanine, norleucine, and phenylglycine.
14. The modified PNA molecule of claim 5 wherein the non-charged amino acids and amino acid analogs are selected from the group consisting of Ala, Val, Leu, Ile, Pro, Phe, Trp, Met and the non-naturally occurring non-polar amino acids β-cyclohexylalanine, 4-chlorophenylalanine, and norleucine.
15. The modified PNA molecule of claim 5 wherein the total number of amino acids and/or amino acid analogs is 15 or less.
16. The modified PNA molecule of claim 5 wherein the total number of amino acids and/or amino acid analogs is 12 or less.
17. The modified PNA molecule of claim 5 wherein the total number of amino acids and/or amino acid analogs is 10 or less.
18. The modified PNA molecule of claim 5 wherein the Peptide is (KFF)3K (SEQ ID NO: 161) or subunits thereof comprising at least 3 amino acids.
19. The modified PNA molecule of claim 18 wherein the Peptide is (KFF)3 (SEQ ID NO: 1.
20. The modified PNA molecule of claim 5 wherein the Peptide is selected from the group consisting of FFRFFRFFR (SEQ ID NO: 6), LLKLLKLLK (SEQ ID NO: 7), LLRLLRLLR (SEQ ID NO: 8), LLKKLAKAL (SEQ ID NO: 9), KFKVKFVVKK (SEQ ID NO: 1), LLKLLLKLLLK (SEQ ID NO: 12), LLKKLAKALK (SEQ ID NO: 13), RRLFPWWWPFRRVC (SEQ ID NO: 14), GRRWPWWPWKWPLIC (SEQ ID NO: 15), LVKKVATTLKKIFSKWKC (SEQ ID NO: 16), KKFKVKFVVKKC (SEQ ID NO: 17), and any subunit thereof comprising at least 3 amino acids, wherein at least one amino acid is a positively charged amino acid.
21. A modified PNA molecule comprising:
H-KFFKFFKFFK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 24) H-FFKFFKFFK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 25) H-FKFFKFFK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 26) H-KFFKLFFK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 27) H-FFKFFK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 28) H-FKFFK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 29) H-KFFK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 30) H-FFK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 31) H-FK-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 32) H-K-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 33) H-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 34) H-KFFKFFKFF-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 35) H-FFKFFKFF-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 36) H-FKFFKFF-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 37) H-KFFKFF-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 38) H-FFKFF-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 39) H-FKFF-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 40) H-KFF-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 41) H-FF-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 42) H-F-ado-CATAGCTGTTTC-NH2, (SEQ ID NO: 43) H-KFFKFFKFFK-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 18) H-KFFKFFKFFK-ado-TGA CTA GAT GAG-NH2, (SEQ ID NO: 44) H-KFFKFFKFFK-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 45) H-FFKFFKFFK-GGC-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 53) H-FFRFFRFFR-GGC-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 54) H-LLKLLKLLK-GGC-Smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 55) H-LLRLLRLLR-GGC-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 56) H-LLKKLAKALK-GC-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 57) H-KRRWPWWPWKK-C-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 58) H-KFKVKFVVKK-GC-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 59) H-LLKLLLKLLLK-C-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 60) H-FFKFFKFFK-GGC-Smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 61) H-KFFKFFKFFK-C-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 62) H-F-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 63) H-FF-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 64) H-KFF-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 65) H-FKFF-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 66) H-FFKFF-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 67) H-KFFKFF-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 68) H-FKFFKFF-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 69) H-FFKFFKFF-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 70) H-KFFKFFKFF-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 71) H-LLKKLAKALKG-ahex-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 21) H-LLKKLAKALKG-ado-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 72) H-KFFKFFKFFK-ado-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 73) H-KFFKFFKFFK-ahex-ado-CCA TCT AAT CCT-NH2, (SEQ JD NO: 74) H2N-KFFKFFKFFK-C-smcc-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 75) H2N-LLKKLAKALK-GC-smcc-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 76) H2N-KFFKFF-C-smcc-ado-CCA TCT AAT CCT-NH2, (SEQ ID NO: 77) H-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 78) H2N-KFFKVKFVVKK-C-smcc-ado-TTC AAA CAT AGT-NH2, (SEQ ID NO: 79) H2N-KFFKVKFVVKK-C-smcc-ado-TTG TGC CCC GTC-NH2, (SEQ ID NO: 80) H2N-KKFKVKFVVKKC-achc-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 81) H-KFFKFFKFFK-achc-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 82) H2N-KKFKVKFVVKKC-lcsmcc-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 83) H2N-KKFKVKFVVKKC-mbs-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 84) H2N-KKFKVKFVVKKC-emcs-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 85) H2N-KKFKVKFVVKKC-smph-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 86) H2N-KKFKVKFVVKKC-amas-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 87) H2N-KKFKVKFVVKKC-smpb-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 88) H2N-KKFKVKFVVKKC-lcsmcc-gly-TTCAAACATAGT-NH2, (SEQ ID NO: 89) H2N-KKFKVKFVVKKC-lcsmcc-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 90) H2N-KKFKVKFVVKKC-lcsmcc-β.cypr-TTCAAACATAGT-NH2, (SEQ ID NO: 91) H2N-KKFKVKFVVKKC-lcsmcc-aha-TTCAAACATAGT-NH2, (SEQ ID NO: 92) H2N-KKFKVKFVVKKC-Icsmcc-adc-TTCAAACATAGT-NH2, (SEQ ID NO: 93) H-KFFKFFKFFK-ado-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 94) H-KFFKFFKFFK-ado-Gly-TTCAAACATAGT-NH2, (SEQ ID NO: 95) H-KFFKFFKFFK-ado-P-TTCAAACATAGT-NH2, (SEQ ID NO: 96) H-KFFKFFKFFK-ado-aha-TTCAAACATAGT-NH2, (SEQ ID NO: 97) H-KFFKFFKFFK-ado-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 98) H-KFFKFFKFFK-ado-achc-TTCAAACATAGT-NH2, (SEQ ID NO: 99) H-KFFKFFKFFK-Gly-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 100) H-KFFKFFKFFK-Gly-Gly-TTCAAACATAGT-NH2, (SEQ ID NO: 101) H-KFFKFFKFFK-Gly-P-TTCAAACATAGT-NH2, (SEQ ID NO: 102) H-KFFKFFKFFK-Gly-aha-TTCAAACATAGT-NH2, (SEQ ID NO: 103) H-KFFKFFKFFK-Gly-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 104) H-KFFKFFKFFK-Gly-achc-TTCAAACATAGT-NH2, (SEQ ID NO: 105) H-KFFKFFKFFK-P-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 106) H-KFFKFFKFFK-P-Gly-TTCAAACATAGT-NH2, (SEQ ID NO: 107) H-KFFKFFKFFK-P-P-TTCAAACATAGT-NH2, (SEQ ID NO: 108) H-KFFKFFKFFK-P-aha-TTCAAACATAGT-NH2, (SEQ ID NO: 109) H-KFFKFFKFFK-P-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 110) H-KFFKFFKFFK-P-achc-TTCAAACATAGT-NH2, (SEQ ID NO: 111) H-KFFKFFKFFK-aha-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 112) H-KFFKFFKFFK-aha-Gly-TTCAAACATAGT-NH2, (SEQ ID NO: 113) H-KFFKFFKFFK-aha-P-TTCAAACATAGT-NH2, (SEQ ID NO: 114) H-KFFKFFKFFK-aha-aha-TTCAAACATAGT-NH2, (SEQ ID NO: 115) H-KFFKFFKFFK-aha-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 116) H-KFFKFFKFFK-aha-achc-TTCAAACATAGTNH2, (SEQ ID NO: 117) H-KFFKFFKFFK-β.ala-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 118) H-KFFKFFKFFK-β.ala-Gly-TTCAAACATAGT-NH2, (SEQ ID NO: 119) H-KFFKFFKFFK-β.ala-P-TTCAAACATAGT-NH2, (SEQ ID NO: 120) H-KFFKFFKFFK-β.ala-aha-TTCAAACATAGT-NH2, (SEQ ID NO: 121) H-KFFKFFKFFK-β.ala-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 122) H-KFFKFFKFFK-β.ala-achc-TTCAAACATAGT-NH2, (SEQ ID NO: 123) H-KFFKFFKFFK-P-p-TTCAAACATAGT-NH2, (SEQ ID NO: 124) H-KFFKFFKFFK-P-P-TTCAAACATAGT-NH2, (SEQ ID NO: 125) H-KFFKFFKFFK-K-K-TTCAAACATAGT-NH2, (SEQ ID NO: 126) H-KFFKFFKFFK-F-F-TTCAAACATAGT-NH2, (SEQ ID NO: 127) H-KFFKFFKFFK-F-K-TTCAAACATAGT-NH2, (SEQ ID NO: 128) H-KFFKFFKFFK-K-F-TTCAAACATAGT-NH2, (SEQ ID NO: 129) H-KFFKFFKFFK-phg-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 130) H-KFFKFFKFFK-phg-Gly-TTCAAACATAGT-NH2, (SEQ ID NO: 131) H-KFFKFFKFFK-phg-P-TTCAAACATAGT-NH2, (SEQ ID NO: 132) H-KFFKFFKFFK-phg-aha-TTCAAACATAGT-NH2, (SEQ ID NO: 133) H-KFFKFFKFFK-phg-β.ala-TTCAAACATAGT-NH2, (SEQ ID NO: 134) H-KFFKFFKFFK-phg-achc-TTCAAACATAGT-NH2, (SEQ ID NO: 135) H-KFFKFFKFFK-achc-ado-TTCAAACATAGT-NH2, (SEQ ID NO: 136) H-KFFKFFKFFK-achc-Gly-TTCAAACATAGT-NH2, (SEQ ID NO: 137) H-KFFKFFKFFK-achc-P-TTCAAACATAGT-NH2, (SEQ ID NO: 138) H-KFFKFFKFFK-achc-aha-TTCAAACATAGT-NH2, (SEQ ID NO: 139) H-KFFKFFKFFK-achc-β.ala-TTCAAACATAGT-NH2, or (SEQ ID NO: 140) H-KFFKFFKFFK-achc-achc-TTCAAACATAGT-NH2. (SEQ ID NO: 141)
22. The modified PNA molecule of claim 5 wherein the PNA sequence is complementary to at least one nucleotide sequence in a bacterium.
23. The modified PNA molecule of claim 22 wherein the PNA sequence is complementary to at least one ribosomal RNA sequence, messenger RNA sequence, or DNA sequence in said bacterium.
24. The modified PNA molecule of claim 5 wherein the PNA sequence is in a parallel or anti-parallel orientation.
25. The modified PNA of claim 22 wherein said at least one nucleotide sequence is essential for the survival of said bacterium and said PNA sequence inhibits the function of said at least one nucleotide sequence.
26. The modified PNA molecule of claim 5 wherein said PNA sequence comprises from 5 to 20 nucleobases.
27. The modified PNA molecule of claim 5 wherein said PNA sequence comprises from 7 to 15 nucleobases.
28. The modified PNA molecule of claim 5 wherein said PNA sequence comprises from 8 to 12 nucleobases.
29. A modified PNA molecule comprising:
H-KFFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCCTCTC-Lys-NH2, (SEQ ID NO: 22) H-KFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH2, (SEQ ID NO: 46) H-FKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH2, (SEQ ID NO: 47) H-FFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH2, (SEQ ID NO: 48) H-KFFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH2, (SEQ ID NO: 49) H-FKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH2, (SEQ ID NO: 50) H-FFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH2, or (SEQ ID NO: 51) H-KFFKFFKFF-ado-JTJTJJT-ado-ado-ado-TCCTCTC-Lys-NH2. (SEQ ID NO: 52)
30. A composition comprising the modified PNA molecule of claim 5 or a pharmaceutically acceptable salt thereof.
31. The composition of claim 30 further comprising an antibiotic.
32. A composition comprising two or more modified PNA molecules of claim 5 or pharmaceutically acceptable salts thereof.
33. The composition of claim 32 further comprising an antibiotic.
34. A method of treating an infectious disease in a mammal comprising administering an effective amount of a modified PNA molecule of claim 5 to said mammal.
35. The method of claim 34 wherein said infectious disease is a bacterial infection.
36. A method of treating an infectious disease in a mammal comprising administering an effective amount of modified oligonucleotide of claim 1 to said mammal.
37. The method of claim 36 wherein said infectious disease is a bacterial infection.
38. A method of treating an infectious disease in a mammal comprising administering an effective amount of a composition of claim 30 to said mammal.
39. A method of treating an infectious disease in a mammal comprising administering an effective amount of a composition of claim 32 to said mammal.
40. A method of identifying a PNA sequence in a PNA molecule useful for inhibiting or reducing growth of at least one bacterium comprising:
contacting a first bacterium with a first modified PNA molecule of claim 5 having a first PNA sequence, wherein said PNA sequence is complementary to at least one nucleotide sequence in said first bacterium;
contacting a second bacterium with a second modified PNA molecule of claim 5 having a second PNA sequence, wherein said PNA sequence is complementary to at least one nucleotide sequence in said second bacterium; and
identifying which PNA sequence is more effective in inhibiting or reducing growth of said bacterium.
41. The method of claim 40 wherein said first and second PNA molecules are identical except for said PNA sequence, and said first and second bacterium are the same species.
42. A method for disinfecting a non-living object comprising contacting said object with a modified oligonucleotide of claim 1.
43. A method for disinfecting a non-living object comprising contacting said object with a modified PNA molecule of claim 5.
44. A method for disinfecting a non-living object comprising contacting said object with a composition comprising a modified oligonucleotide of claim 1.
45. A method for disinfecting a non-living object comprising contacting said object with a composition comprising a modified PNA molecule of claim 5.
46. The method of claim 42 wherein said object is a surgery tool, hospital inventory, dental tool, slaughterhouse inventory, slaughterhouse tool, dairy inventory, or dairy tool.
47. The method of claim 43 wherein said object is a surgery tool, hospital inventory, dental tool, slaughterhouse inventory, slaughterhouse tool, dairy inventory, or dairy tool.
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