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WO2009077173A3 - Dna-encoded chemical libraries - Google Patents

Dna-encoded chemical libraries Download PDF

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Publication number
WO2009077173A3
WO2009077173A3 PCT/EP2008/010770 EP2008010770W WO2009077173A3 WO 2009077173 A3 WO2009077173 A3 WO 2009077173A3 EP 2008010770 W EP2008010770 W EP 2008010770W WO 2009077173 A3 WO2009077173 A3 WO 2009077173A3
Authority
WO
WIPO (PCT)
Prior art keywords
complementary
region
single strand
coding
initial
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2008/010770
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French (fr)
Other versions
WO2009077173A2 (en
Inventor
Dario Neri
Samu Melkko
Luca Mannoci
Fabian Buller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Philochem AG
Original Assignee
Philochem AG
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Publication date
Application filed by Philochem AG filed Critical Philochem AG
Publication of WO2009077173A2 publication Critical patent/WO2009077173A2/en
Publication of WO2009077173A3 publication Critical patent/WO2009077173A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102Mutagenizing nucleic acids
    • C12N15/1031Mutagenizing nucleic acids mutagenesis by gene assembly, e.g. assembly by oligonucleotide extension PCR
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034Isolating an individual clone by screening libraries
    • C12N15/1068Template (nucleic acid) mediated chemical library synthesis, e.g. chemical and enzymatical DNA-templated organic molecule synthesis, libraries prepared by non ribosomal polypeptide synthesis [NRPS], DNA/RNA-polymerase mediated polypeptide synthesis

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  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Plant Pathology (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

A method of preparing a DNA-encoded chemical library comprising members which comprise a chemical moiety, a linking moiety and a DNA moiety, comprising for each member the steps of: (I) coupling a initial building block to a initial coding single strand oligomer via a linking moiety to form a initial conjugate, the initial coding single strand oligomer comprising a first primer region, an initial coding region and a first annealing region; (II) optionally coupling a middle building block and middle coding single strand oligomer to said initial conjugate to form a middle conjugate, the coupling take place in either order, wherein: (a) the middle building block is coupled to the residue of the initial building block; and (b) the middle coding single strand oligomer comprises a middle coding region and second annealing region, and is coupled by: (i) annealing a complementary single strand oligomer which comprises a chemical modifier, a complementary first annealing region, a complementary middle coding region and a complementary second annealing region by interaction between the first annealing region and the complementary first annealing region; (ii) treating the conjugate formed with a DNA polymerase to elongate the initial coding single strand oligomer to be complementary to the complementary middle coding region and the complementary second annealing region; (iii) removing the complementary single strand oligomer by denaturing the DNA and capturing the complementary single strand oligomer via the chemical modifier; (III) coupling a final building block and final coding single strand oligomer to the initial or middle conjugate as appropriate to form a final conjugate, the coupling take place in either order, wherein: (a) the final building block is coupled to the residue of the initial building block, or may be additionally or alternatively be coupled to the residue of the middle building block (if present); and (b) the final coding single strand oligomer comprises a final coding region and a second primer region, and is coupled by: (i) annealing a complementary single strand oligomer which comprises a complementary first or second annealing region as appropriate, a complementary final coding region and a complementary second primer region, by interaction between the first or second annealing region and the complementary first or second annealing region, as appropriate; (ii) treating the conjugate formed with a DNA polymerase to elongate the initial coding single strand oligomer to be complementary to the complementary final coding region and the complementary second primer region, and to elongate the complementary coding strand to be complementary to the initial coding single strand oligomer.
PCT/EP2008/010770 2007-12-19 2008-12-17 Dna-encoded chemical libraries Ceased WO2009077173A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US824907P 2007-12-19 2007-12-19
US61/008,249 2007-12-19

Publications (2)

Publication Number Publication Date
WO2009077173A2 WO2009077173A2 (en) 2009-06-25
WO2009077173A3 true WO2009077173A3 (en) 2009-10-29

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/010770 Ceased WO2009077173A2 (en) 2007-12-19 2008-12-17 Dna-encoded chemical libraries

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WO (1) WO2009077173A2 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8932992B2 (en) 2001-06-20 2015-01-13 Nuevolution A/S Templated molecules and methods for using such molecules
US9096951B2 (en) 2003-02-21 2015-08-04 Nuevolution A/S Method for producing second-generation library
US9109248B2 (en) 2002-10-30 2015-08-18 Nuevolution A/S Method for the synthesis of a bifunctional complex
US9121110B2 (en) 2002-12-19 2015-09-01 Nuevolution A/S Quasirandom structure and function guided synthesis methods
US9574189B2 (en) 2005-12-01 2017-02-21 Nuevolution A/S Enzymatic encoding methods for efficient synthesis of large libraries

Families Citing this family (36)

* Cited by examiner, † Cited by third party
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WO2003078625A2 (en) 2002-03-15 2003-09-25 Nuevolution A/S An improved method for synthesising templated molecules
US10730906B2 (en) 2002-08-01 2020-08-04 Nuevolutions A/S Multi-step synthesis of templated molecules
ATE447626T1 (en) 2003-09-18 2009-11-15 Nuevolution As METHOD FOR OBTAINING STRUCTURAL INFORMATION FROM ENCODED MOLECULES AND FOR SELECTING COMPOUNDS
EP2361930A3 (en) 2007-03-26 2011-10-26 Dako Denmark A/S Multimers of MHC-peptide complexes and uses thereof in Borrelia infectious diseases
WO2009003493A2 (en) 2007-07-03 2009-01-08 Dako Denmark A/S Mhc multimers, methods for their generation, labeling and use
EP2197908A2 (en) 2007-09-27 2010-06-23 Dako Denmark A/S Mhc multimers in tuberculosis diagnostics, vaccine and therapeutics
WO2010009735A2 (en) 2008-07-23 2010-01-28 Dako Denmark A/S Combinatorial analysis and repair
WO2010037402A1 (en) 2008-10-02 2010-04-08 Dako Denmark A/S Molecular vaccines for infectious disease
US11992518B2 (en) 2008-10-02 2024-05-28 Agilent Technologies, Inc. Molecular vaccines for infectious disease
ES2842527T3 (en) 2009-02-13 2021-07-14 X Chem Inc Methods for creating and analyzing DNA-encoded libraries
US8329239B2 (en) * 2009-03-03 2012-12-11 Givandan S.A. Off-taste masking
CA2832672A1 (en) 2010-04-16 2011-10-20 Nuevolution A/S Bi-functional complexes and methods for making and using such complexes
WO2012019765A1 (en) * 2010-08-10 2012-02-16 European Molecular Biology Laboratory (Embl) Methods and systems for tracking samples and sample combinations
WO2013036810A1 (en) 2011-09-07 2013-03-14 X-Chem, Inc. Methods for tagging dna-encoded libraries
ES2675167T3 (en) * 2012-07-13 2018-07-09 X-Chem, Inc. DNA-encoded libraries that have non-polymerase readable oligonucleotide linkages
GB201322692D0 (en) 2013-12-20 2014-02-05 Philochem Ag Production of encoded chemical libraries
EP3102241B1 (en) 2014-02-03 2019-04-17 Eidgenössiche Technische Hochschule Zürich Small molecule drug conjugates
GB201404552D0 (en) * 2014-03-14 2014-04-30 Philochem Ag Purification of dna-conjugate products
DK3152232T3 (en) * 2014-06-06 2020-02-24 Immudex Aps Determination of antigen recognition by bar coding of MHC multimers
WO2015188839A2 (en) 2014-06-13 2015-12-17 Immudex Aps General detection and isolation of specific cells by binding of labeled molecules
US20180340174A1 (en) 2014-11-11 2018-11-29 Nanocore Aps Method for identification of molecules with desired characteristics
US11576892B2 (en) 2015-08-18 2023-02-14 Novation Pharmaceuticals Inc. Benzopyran derivatives and uses thereof
CN105218405B (en) * 2015-11-04 2017-07-28 上海泰坦科技股份有限公司 The synthesis technique of (R, S) 2 [[base of 5 (9 fluorenylmethyloxycarbonyl amino) dibenzo [A, D] cycloheptane 2] oxygen] acetic acid
GB201603789D0 (en) 2016-03-04 2016-04-20 Apta Biosciences Ltd Oligonucleotides and methods for preparing
CN115820806A (en) 2016-06-16 2023-03-21 哈斯达克科学公司 Combinatorial synthesis of oligonucleotide-guided and documented encoded probe molecules
WO2018089641A2 (en) * 2016-11-10 2018-05-17 The Scripps Research Institute Encode solid phase compound library with polynucleotide based barcoding
WO2018204420A1 (en) 2017-05-02 2018-11-08 Haystack Sciences Corporation Molecules for verifying oligonucleotide directed combinatorial synthesis and methods of making and using the same
RU2020112854A (en) 2017-11-30 2021-12-30 Арракис Терапьютикс, Инк. PHOTOPROBES BINDING NUCLEIC ACIDS AND METHODS OF THEIR APPLICATION
CN108178790B (en) * 2018-01-18 2021-09-07 上海药明康德新药开发有限公司 Method for separating cell membrane to screen transmembrane protein by using DNA coding compound library
WO2019149198A1 (en) * 2018-01-31 2019-08-08 成都先导药物开发股份有限公司 Dna-encoded compound library and compound screening method
WO2019236644A1 (en) * 2018-06-05 2019-12-12 Arrakis Therapeutics, Inc. Encoded libraries and methods of use for screening nucleic acid targets
WO2020047095A1 (en) * 2018-08-28 2020-03-05 The Scripps Research Institute Use of non-covalent immobilization in dna encoded libraries
GB201821109D0 (en) 2018-12-21 2019-02-06 Philochem Ag Nucleic acid encoded chemical libraries
CN112575389B (en) * 2019-09-30 2023-09-19 成都先导药物开发股份有限公司 Liquid chromatography purification method of DNA coding compound library
EP4232578A1 (en) 2020-10-23 2023-08-30 ETH Zurich Self-purified nucleic acid encoded libraries
WO2024254528A1 (en) * 2023-06-09 2024-12-12 Arc Institute Methods of screening for sting inhibitors

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Patent Citations (1)

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Non-Patent Citations (8)

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Title
BULLER F ET AL: "Design and synthesis of a novel DNA-encoded chemical library using Diels-Alder cycloadditions", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, ELSEVIER SCIENCE, GB, vol. 18, no. 22, 15 November 2008 (2008-11-15), pages 5926 - 5931, XP025627172, ISSN: 0960-894X, [retrieved on 20080715] *
GARTNER Z J ET AL: "DNA-templated organic synthesis and selection of a library of macrocycles", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, WASHINGTON, DC, vol. 305, no. 5690, 10 September 2004 (2004-09-10), pages 1601 - 1605, XP002397753, ISSN: 0036-8075 *
HALPIN DAVID R ET AL: "DNA display II. Genetic manipulation of combinatorial chemistry libraries for small-molecule evolution", PLOS BIOLOGY, PUBLIC LIBRARY OF SCIENCE, US, vol. 2, no. 7, 1 July 2004 (2004-07-01), pages 1022 - 1030, XP002424416, ISSN: 1544-9173 *
MANNOCCI LUCA ET AL: "High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 105, no. 46, November 2008 (2008-11-01), pages 17670 - 17675, XP002541365, ISSN: 0027-8424 *
MELKKO ET AL: "Lead discovery by DNA-encoded chemical libraries", DRUG DISCOVERY TODAY, ELSEVIER, RAHWAY, NJ, US, vol. 12, no. 11-12, 1 June 2007 (2007-06-01), pages 465 - 471, XP022095609, ISSN: 1359-6446 *
MELKKO S ET AL: "Encoded self-assembling chemical libraries", NATURE BIOTECHNOLOGY MAY 2004 NATURE PUBLISHING GROUP US, vol. 22, no. 5, May 2004 (2004-05-01), pages 568 - 574, XP002541364 *
SCHEUERMANN J ET AL: "DNA-encoded chemical libraries", JOURNAL OF BIOTECHNOLOGY, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 126, no. 4, 1 December 2006 (2006-12-01), pages 568 - 581, XP024956589, ISSN: 0168-1656, [retrieved on 20061201] *
TENG S F ET AL: "A STRATEGY FOR THE GENERATION OF BIOMIMETIC LIGANDS FOR AFFINITY CHROMATOGRAPHY. COMBINATORIAL SYNTHESIS AND BIOLOGICAL EVALUATION OF AN IGG BINDING LIGAND", JOURNAL OF MOLECULAR RECOGNITION, HEYDEN & SON LTD., LONDON, GB, vol. 12, no. 1, 1 January 1999 (1999-01-01), pages 67 - 75, XP001084821, ISSN: 0952-3499 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8932992B2 (en) 2001-06-20 2015-01-13 Nuevolution A/S Templated molecules and methods for using such molecules
US9109248B2 (en) 2002-10-30 2015-08-18 Nuevolution A/S Method for the synthesis of a bifunctional complex
US9284600B2 (en) 2002-10-30 2016-03-15 Neuvolution A/S Method for the synthesis of a bifunctional complex
US9121110B2 (en) 2002-12-19 2015-09-01 Nuevolution A/S Quasirandom structure and function guided synthesis methods
US9096951B2 (en) 2003-02-21 2015-08-04 Nuevolution A/S Method for producing second-generation library
US9574189B2 (en) 2005-12-01 2017-02-21 Nuevolution A/S Enzymatic encoding methods for efficient synthesis of large libraries

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