MXPA99010560A

MXPA99010560A - Detergent compositions

Info

Publication number: MXPA99010560A
Application number: MXPA/A/1999/010560A
Authority: MX
Inventors: Mohamed Khan Sarnaik Khizar; Minamikawa Kaori
Original assignee: Minamikawa Kaori; Mohamed Khan Sarnaik Khizar; The Procter & Gamble Company
Priority date: 1997-05-16
Filing date: 1999-11-16
Publication date: 2000-09-04

Abstract

A detergent composition comprising a soil dispersant polymer, a non-bis AQA surfactant and a bis-alkoxylated quaternary ammonium (bis-AQA) cationic surfactant, wherein the weight ratio of the bis-AQA to the soil dispersant polymer is in the range of from 1:11 to 1:14.

Description

PEPTIDE ANALOGS OF HORMONE PARATIRODEA TECHNICAL FIELD This invention is directed to compounds and their preparation; to pharmaceutical compositions containing the compounds and to their use in the treatment of physiological conditions capable of being modulated by agonist or antagonist activity on parathyroid hormone receptors. More particularly, this invention is directed to peptide analogues of parathyroid hormone and peptide protein analogs, related to parathyroid hormone.

BACKGROUND OF THE INVENTION Human parathyroid hormone (hPTH) is a protein of 84 amino acids, which is a major regulator of calcium homeostasis. The protein related to parathyroid hormone (hPTHrP) is a protein of 139 to 171 amino acids, with N-terminal homology with hPTH. The N-terminal fragments of hPTH and hPTHrP, particularly those consisting of amino acids 1-34, retain the full biological activity of the major hormone. HPTH (1-34) has the following amino acid sequence: Ser-Val-Ser-Glu-lle-GIn-Leu-Met-His-Asn-Lys-Gly-Lys-His-Leu-Asn-Ser-Met-Glu-Arg-Val-Glu-Trp-Leu-Arg- Lys-Lys-Leu-Gln-Asp-Val-His-Asn-Phe (SEQ ID NO: 1) hPTHrP has the following amino acid sequence: Ala-Val-Ser-Glu-His-GIn-Leu-Leu-His -Asp-Lys-Gly-Lys-Ser-lle-GIn-Asp-Leu-Arg-Arg-Arg-Phe-Phe-Leu-His-His-Leu-lle-Ala-Glu-IIe-His-Thr-Ala (SEQ ID NO: 2) The biological activity of hPTH is reflected in the activation of two secondary messenger systems: adenylyl cyclase (AC) coupled to protein G, and the activity of protein kinase C (PKC) coupled and uncoupled to protein G. It has been shown that the N-terminal fragments hPTH (1-34) and hPTH (1-31) NH2 are anabolic with respect to skeletal formation in humans and in ovarianized rats, respectively. This increase in bone growth has been shown to be coupled with the stimulation of adenylyl cyclase activity. Analogs of these N-terminal fragments have significant therapeutic potential for the treatment of physiological conditions associated with the regulation of calcium in bone cells, including hypocalcemia, osteoporosis, osteopenia and disorders associated with osteoporosis and osteopenia, such as hyperparathyroidism, hypoparathyroidism and Cuchings syndrome; Osteopenia induced by glucocorticoids and induced by immunosuppressants; and repair of bone fracture and bone refracture.

It has also been established that the omission of up to six amino acid residues from the N-terminus of hPTH (1-34) markedly decreases the ability of the resulting analog to stimulate adenylyl cyclase, while having little effect on receptor binding. Thus, hPTH analogs (1-34) truncated in up to six amino acid residues at the N-terminus inhibit the action of PTH and are useful in the treatment of disorders characterized by an excess of PTH, such as a hypercalcemia-related crisis. with hyperparathyroidism and hyperparathyroidism, malignant hypercalcemia, renal failure and hypertension. Acyclic analogues of hPTH (1-27) to (1-34) are disclosed in US Patent 4,086,196. Acyclic analogs of hPTH (1-34) and hPTHrP (1-34) are disclosed in U.S. Patent No. 5,589,452. They are described [Nie8, Nie18, Tyr34 or Phe34] hPTH (1-34) in U.S. Patent 4,656,250. They are described [Nie8, Nie18, Tyr34] h PTH (1-34) and their N-truncated derivatives are described in US Patents 4,771, 124 and 4,423,037. Other acyclic analogs of PTH (1-34) are described in U.S. Patent Nos. 5,723,577 and 5,434,246, WO 97/02834, EPA 561 412-A1, EPA 747 817-A2, WO-94/02510, WO9603437 and WO951 1988- A1. Analogs of hPTH (1-28) NH2 to hPTH (1-31) NH2 and [Leu27] hPTH (1-28) NH2 to [Leu27] hPTH (1-33) NH2 are described in U.S. Patent 5,556,940. Acyclic PTH receptor antagonists, including N-terminally truncated PTH analogs, are described in U.S. Patents 5,446,130, 5,229,489, 4,771, 124 and 4,423,037. Cyclic and bicyclic analogues of hPTH and hPTHrP have been described. Cyclo (Lys26-Asp30) [Leu27] hPTH (1-34) NH2 and cyclo (Lys27-Asp30) hPTH (1-34) NH2 are described in U.S. Patent No. 5,556,940. Cycle (Lys26-Asp-30) [Leu27] hPTH (1-31) NH2, cycle (Glu22-Lys26) [Leu27] hPTH (1-31) NH2, and cycle (Lys27-Asp30) hPTH (1-31) are described ) NH2 by Barbier and co-authors, J. Med. Chem., 1997, 40, 1373. The monocyclic and bicyclic derivatives of hPTH (1-34) or hPTHrP (1-34) are described in WO 96/40193 , DE19508672-A1 and by A. Bisello and co-authors, in Biochemistry 1997, 36, 3293. The cycle (Lys13-Asp17) hPTHrP (7-34) NH2, a potent PTH receptor antagonist, is described by M. Chorev and coauthors, Biochemistry 1991, 30, 5698. Also Kanmera and coauthors have described a series of hPTHrP analogues containing amide, Peptide Chemistry 1993: Okada, Y., ed .; Protein Research Foundation, Osaka, 1994, 321-324.

BRIEF DESCRIPTION OF THE INVENTION This invention is directed to a cyclic peptide compound of the formula I: XA? O-A11-Ai2-A13-A14-A15-A16-A17-A18-Ai9-A2o-A2? -A22-A23-A2 -A25-A26 -A27-Y or a pharmaceutically acceptable salt or prodrug thereof; wherein X is selected from the group consisting of: (a) Ria-Ao-A1-A2-A3-A4-A5-A6-A7-A8-A9-, (c) Rib-A3-A4-A5-A6-A7-A8-A9-, (d) Ria-A4-A5-A6-A7-A8-A9-, (e) R1a-A5-A6-A7-A8 -A9-, (f) R1a-A6-A7-A8-A9-, (g) R1a-A7-A8-A9-, (h) Ria-A8-A9-, (i) Ria-A9- and (j) ) Ría-; And it is selected from the group consisting of: (a) -R3, (b) -A28-R3, (c) -A28-A29-R3, (e) -A28-A29-A3o-A3? -R3, (f) -A28-A29-A30-A3i-A32-R3 > (g) -A28-A29-A3o-A3i-A32-A33-R3. and (h) -A28-A29-A30-A3i-A32-A33-A34-R3; R-a is H, alkyl, aralkyl or -COR2; Rib is R? A or a group of the formula: R2 is alkyl, alkenyl, alkynyl, aryl or aralkyl; R3 is a group of the formula A35-OR or A35-NR4R5; R4 and R5 are independently H or lower alkyl; R6 and Rg are independently H or alkyl; R7 is alkyl; R8 is H, alkyl or COR2; R10 is H or halogen; R11 is alkyl or aralkyl; m is 1, 2 or 3; n is 3 or 4; Ao is absent or is a peptide of 1 to 6 amino acid residues; A-i is Ser, Ala, Gly or D-Pro, or an amino acid equivalent to them; A2 is Ala, Val or Gly, or an amino acid equivalent to them; A3 is Ala, Ser, Gly or D-Pro, or an amino acid equivalent to them; A4 is Glu, Ala or Gly, or an equivalent amino acid thereof; A5 is Lie, His, Ala or Gly, or an amino acid equivalent to them; Aß is Ala, Gln, Gly or D-Pro, or an amino acid equivalent to them; A is Ala, Leu, Gly or an amino acid equivalent to them; A8 is Leu, Nie, Gly or D-Pro, or an amino acid equivalent thereof; A9 is His, Ala, D-Pro or Gly, or an amino acid equivalent thereof; A10 is Ala, Asn, Asp, Cys, homo-Cys, Glu, Gly, Lys, Orn, Ser, Thr, D-Pro, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; Ai-i is Ala, Gly, Leu or Lys or an equivalent amino acid thereof; A-? 2 is Ala or Gly, or an equivalent amino acid thereof; A13 is Ala, Asn, Asp, Cys, homo-Cys, Glu, Gly, Lys, Orn, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; AM is Ala, Asn, Asp, Cys, homo-Cys, Glu, Gly, His, Lys, Orn, Ser, Thr, D-Pro, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; A-? 5 is Ala, Gly, lie, D-Pro or Leu, or an equivalent amino acid thereof; A-I6 is Asn, Ala, Gly, D-Pro or Gln or an equivalent amino acid thereof; A? 7 is Ala, Asn, Asp, Cys, homo-Cys, Glu, Gly, Lys, Orn, Ser, Thr, D-Pro, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; A? 8 is Asp, Cys, homo-Cys-Glu, His, Leu, Lys, Orn, Nie, Ser, Thr, -NHCH (CH 2) p.NH 2) CO- or -NHCH [(CH 2) nCO 2 H] CO-; A-ig is Arg or Glu or an amino acid equivalent to them; A2o is Arg or an equivalent amino acid thereof; A21 is Arg, Asp, Cys, homo-Cys, Glu, Lys, Orn, Ser, Thr, Val, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; A22 is Asp, Cys, homo-Cys-Glu-His, Lys, Orn, Phe, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CH-; A23 is Leu, Phe or Trp, or an amino acid equivalent to them; A24 is Leu or an equivalent amino acid thereof; A25 is Arg, Asp, Cys, homo-Cys, Glu, His, Lys, Orn, D-Pro, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; A2T is Asp, Cys, homo-Cys, Glu, His, Lys, Orn, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; A27 is Leu or Lys, or an amino acid equivalent to them; A28 is either Leu or an amino acid equivalent to them; A2g is Ala, Asp, Cys, homo-Cys, Glu, Gln, Lys, Orn, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; A30 is Asp, Cys, homo-Cys, Glu, Gly, Lys, Orn, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nCO2H] CO-; A31 is Lie, Leu or Val or an equivalent amino acid of them; A32 is His or an equivalent amino acid thereof; A33 is Asn or Thr, or an amino acid equivalent to it; Y A3 is Ala or Phe, or an amino acid equivalent to them; A35 is absent or is a peptide of 1 to 4 amino acids; and the side chains of at least one of the following pairs of amino acid residues A10 and A-? 4, A13 and A17, A and A-? 8 > A17 and A2- ?, A-? 8 and A22, A2? and A25, A25 and A2g and A2β and A30 are linked by means of an amide, ester, disulfide or lanthionine bond to form a bridge; and the side chain of each of the following amino acid residues: A10, A13, A-u, A? , A-? 8, A2 ?, A22, A25, A26, A2g and A30 contributes, at most, to the formation of a single bridge; provided that, when the side chains of the following pairs of amino acid residues, A13 and A17 or A26 and A30 are linked through an amide, disulfide or lanthionine linkage, to form a bridge; then the side chains of at least one of the following pairs of amino acid residues, A10 and A14, A14 and A18, A17 and A21, A18 and A22, A21 and A25 and A25 and A2g are also linked through an amide, ester, disulfide or lanthionine ligature. In another aspect, this invention is directed to a peptide compound of formula II: X-A1o-A1? -A12-Ai3-A14-A15-A? 6-A17-Ai8-A19-A2o-A2? -A22-A23-A24-A25-A26-A27-Y (II) or a pharmaceutically acceptable salt or prodrug thereof, wherein X is selected from the group consisting of: (a) R1a-Ao-A1-A2-A3-A4-A5-A6-A7-A8-A9-; (b) R1a-A2-A3-A4-A5-A6-A7-A8-A9-; (c) R1b-A3-A4-A5-A6-A7-A8-A9-; (d) Ri a-A4-A5-A6-A7-A8-Ag-; (e) ia-A5-A6-A7-A8-A9-; (f) R1a-A6-A7-A8-A9-; (g) A1a-A7-A8-A9-; (¡) R.a-A9-; and (j) R .a. And it is selected from the group consisting of (a) -R3, (b) - A28-R3, (e) -A28-A29-A30-A31-3; (f) -A28-A2 -A3o-A31 -A32- R3; (g) -A28-A2g-A3o-A3l-A32-A33-3; and (h) -A28-A29-A3o-A3i-A32-A33-A3 -R3; R-a is H, alkyl, aralkyl or -COR2; R b is R-ia or a group of the formula: R2 is alkyl, alkenyl, alkynyl, aryl or aralkyl; R3 is a group of the formula A35-OR4 or A35-NR4R5; R4 and R5 are independently H or lower alkyl; Re and Rg are independently H or alkyl; R7 is alkyl; R8 is H, alkyl or COR2; R10 is H or halogen; R-11 is alkyl or aralkyl; Ao is absent or is a peptide of 1 to 6 amino acid residues; A-i is Ser, Ala, Gly or D-Pro, or an equivalent amino acid thereof; A2 is Ala, Val or Gly, or an equivalent amino acid thereof; A3 is Ala, Ser, Gly or D-Pro, or an equivalent amino acid thereof; A4 is Glu, Ala or Gly or an amino acid equivalent to them; A5 is Lie, His, Ala or Gly or an equivalent amino acid thereof; AQ is Ala, Gln, Gly or D-Pro; or an equivalent amino acid of them; A7 is Ala, Leu or Gly, or an amino acid equivalent to them; A8 is Leu, Nie, Gly or D-Pro, or an amino acid equivalent thereof; Ag is His, Ala, Gly or D-Pro, or an amino acid equivalent thereof; A10 is Ala, Asn, Gly, Lys, Asp or D-Pro, or an amino acid equivalent to them; An is Ala, Gly, Leu or Lys, or an equivalent amino acid of them; A-.2 is Ala or Gly or an amino acid equivalent to them; A-Í3 is Ala, Gly or Lys, or an amino acid equivalent to them; A14 is Ala, Gly, His, Ser, Asp, Lys or D-Pro, or an amino acid equivalent to them; A? 5 is Ala, Gly, lie, D-Pro or Leu, or an amino acid equivalent to them; A-I6 is Asn, Ala, Gly, D-Pro or Gln, or an amino acid equivalent thereto; A-? 7 is Ala, Asp, Gly, Ser, Lys or D-Pro, or an amino acid equivalent thereto; A-is is Lys or an amino acid equivalent to them; A-19 is Arg or Glu, or an amino acid equivalent to them; A2o is Arg, or an equivalent amino acid thereof; A2? is Arg, Lys, Asp or Val, or an equivalent amino acid thereof; A22 is Asp, Lys, Orn or Glu, or an equivalent amino acid thereof; A23 is Leu, Phe or Trp, or an amino acid equivalent to them; A2 is Leu or an equivalent amino acid thereof; A25 is Arg, His, Asp, Lys or Glu, or an amino acid equivalent thereof; A26 is Lys or His, or an amino acid equivalent to them; A2 is Leu or Lys, or an amino acid equivalent to them; A28 is lie or Leu, or an amino acid equivalent to them; A2g is Ala, Asp, Glu or Gln, or an equivalent amino acid thereof; A30 is Asp, Lys or Glu, or an amino acid equivalent to them; A31 is He, Leu or Val, or an amino acid equivalent to them; A32 is His or an equivalent amino acid thereof; A33 is Asn or Thr, or an amino acid equivalent to them; and A3 is Ala or Phe, or an amino acid equivalent thereto; and A35 is absent or is a peptide of 1 to 4 amino acids. The peptide compounds of the present invention possess useful properties, more in particular, pharmaceutical properties. They are especially useful for treating disease states capable of being modulated by compounds that bind to parathyroid hormone receptors, either with or without concomitant stimulation of adenylyl cyclase activity. Accordingly, the present invention is also directed to the pharmaceutical use of the peptide compounds and pharmaceutical compositions containing the peptide compounds.

DETAILED DESCRIPTION OF THE INVENTION As used in the foregoing and used throughout the specification, it will be understood that the following terms, unless otherwise indicated, have the following meanings: DEFINITIONS OF TERMS "Patient" includes both humans and other mammals. "Alkyl" means an aliphatic hydrocarbon group which may be straight or branched chain, having about 1 to 20 carbon atoms in the chain. Branched means that one or more lower alkyl groups are attached to a linear alkyl chain. "Lower alkyl" means about 1 to 4 carbon atoms in the chain, which may be straight or branched. Alkyl groups are exemplified by methyl, ethyl, n-e-sopropyl, n-, sec- and tert-butyl, and the like.

"Alkenyl" means an aliphatic hydrocarbon group containing a double bond of carbon to carbon and which may be straight or branched, having about 2 to 20 carbon atoms in the chain.

"Lower alkenyl" means about 2 to 4 carbon atoms in the chain, which may be straight or branched. Exemplary alkenyl groups include: ethenyl, propenyl, n-butenyl, isobutenyl, 3-methylbut-2-enyl, n-pentenyl, heptenyl, octenyl, cyclohexylbutenyl and decenyl. "Alkynyl" means an aliphatic hydrocarbon group containing a triple carbon to carbon ligation and which may be straight or branched, having about 2 to 20 carbon atoms in the chain. "Lower alkynyl" means about 2 to 4 carbon atoms in the chain, which may be straight or branched. Examples of alkynyl groups include: ethynyl, propynyl, n-butynyl, 3-methylbut-2-ynyl, n-pentynyl, heptynyl, octynyl and decynyl. "Alkylene" denotes a divalent group derived from a saturated hydrocarbon, straight or branched chain, by separation of two hydrogen atoms, for example: methylene, 1,2-ethylene, 1,1-ethylene, 1,3-propylene, 2,2-dimethylpropylene and the like. "Aralkyl" means an aryl group attached to the original molecular moiety, through an alkylene. Preferred aralkyls contain a lower alkyl moiety. Representative aralkyl groups include: benzyl, 2-phenethyl, naphthylmethyl and the like. A preferred aralkyl group is benzyl.

"Aryl" means a monocyclic or multicyclic, aromatic ring system, from 6 to about 14 carbon atoms, preferably around 6 to 10 carbon atoms. The aryl is optionally substituted with one or more substituents selected from alkyl, hydroxy, halogen and haloalkyl. Representative aryl groups include phenyl and naphthyl. "Amino acid" means an amino acid selected from the group consisting of the natural and non-natural amino acids, as defined herein. The amino acids can be neutral, positive or negative, depending on the substituents present in the side chain. "Neutral amino acid" means an amino acid that contains uncharged side chain substituents. Examples of neutral amino acids include: alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, methionine, glycine, serine, threonine and cysteine. "Amino acid positive" means an amino acid in which the substituents of the side chain are positively charged at physiological pH. Examples of positive amino acids include: lysine, arginine and histidine. "Negative amino acid" means an amino acid in which the substituents of the side chain carry a net negative charge at physiological pH. Examples of negative amino acids include: aspartic acid and glutamic acid. The preferred amino acids are alpha-amino acids. The most preferred amino acids are alpha-amino acids that have L stereochemistry at the alpha carbon atom. "Natural amino acid" means an alpha-amino acid selected from the group consisting of alanine, valine, leucine, soleucine, proline, phenylalanine, tryptophan, methionine, glycine, serine, threonine, cysteine, tyrosine, asparagine, glutamine, lysine, arginine, histidine, aspartic acid and glutamic acid. "Unnatural amino acid" means an amino acid for which there is no nucleic acid codon. Examples of non-natural amino acids include, for example, the D isomers of the natural alpha-amino acids, such as D-proline (D-P, D-Pro), as indicated above; Aib (aminobutyric acid), bAib (3-aminoisobutyric acid), Nva (norvaline), β-Ala, Aad (2-aminoadipic acid), bAad (3-aminoadipic acid), Abu (2-aminobutyric acid), Gaba (acid gamma-aminobutyric acid), Acp (6-aminocaproic acid), Dbu (2,4-diaminobutyric acid), alpha-aminopimelic acid, TMSA (trimethylsilyl-Ala), alie (alo-isoleucine), Nie (norleucine), Iert-Leu , Cit (citrulline), Orn (ornithine, O), Dpm (2,2'-diaminopimelic acid), Dpr (2,3-diaminopropionic acid), alpha- or beta-Nal, Cha (cyclohexyl-Ala), hydroxyproline, Sar (sarcosine) and the like; cyclic amino acids; Na-alkylated amino acids, such as eGly (Na-methylglycine), EtGly (Na-ethylglycine) and EtAsn (Na-ethylaparagine); and amino acids in which the alpha carbon carries two side chain substituents. "Peptide" and "polypeptide" means a polymer in which the monomers are amino acid residues linked together by means of amide bonds. Preferred peptide compounds of the present invention are those comprising alpha-amino acids. "Compound "peptide" means a compound comprising a peptide as defined herein "Amino acid residue" means the individual amino acid units incorporated into the peptide compounds of the present invention The names of the natural and unnatural amino acids and their residues, used here, they follow the designation conventions suggested by the Commission on the Nomenclature of Organic Chemistry of the IUPAC and the Commission on Biochemical Nomenclature of the IUPAC-IUB, as they appear in "Nomenclature of alpha-Amino Acids (Recommendations, 1974)" , Biochemistry, 14 (2), (1975), insofar as the names and abbreviations of the amino acids and their residues, used in this specification and in the claims that come to the end, differ from those noted, will be clarified Names and abbreviations that differ. "Equivalent amino acid" means an amino acid that can be substituted by another amino acid in peptide compounds. cos according to the invention, without any appreciable loss of function. In making those changes, substitutions of similar amino acids are made on the basis of the relative similarity of the side chain substituents, for example, with respect to size, charge, hydrophilicity, hydropasticity and hydrophobicity, as described herein. . The phrase "or an amino acid equivalent thereof (the same) (them)", when used after a list of Individual amino acids means an equivalent of each of the individual amino acids included in the list. As detailed in U.S. Patent No. 4,554,101, incorporated herein by this reference, it has been assigned to the waste of. amino acid the following hydrophilicity values: Arg (+3.0); Lys (+3.0), Asp (+3.0), Glu (+3.0), Ser (+0.3), Asn (+0.2), Gln (+0.2), Gly (0), Pro (-0.5), Thr (- 0.4), Ala (-0.5), His (-0.5), Cys (-1.0); Met (-1.3), Val (-1.5), Leu (-1.8), He (-1.8), Tyr (-2.3), Phe (-2.5) and Trp (-3.4). It is understood that an amino acid residue can be substituted by another having a similar hydrophilicity value (for example, within a value of plus or minus 2.0) and still obtain a biologically equivalent polypeptide. Similarly, substitutions can be made on the basis of similarity in the hydropathic index. A hydropathic index has been assigned to each amino acid residue on the basis of its hydrophobicity and its loading characteristics. These hydropathic index values are: He (+4.5), Val (+4.2), Leu (+3.8), Phe (+2.8), Cys (+2.5), Met (+1.9), Ala (+1.8), Gly (-0.4); Thr (-0.7), Ser (-0.8), Trp (-0.9) Tyr (-1.3), Pro (-1.6), His (-3.2), Glu (-3.5), Gln (-3.5), Asp (- 3.5), Asn (-3.5), Lys (-3.9) and Arg (-4.5). When performing a substitution based on the hydropathic index, a value is preferred within plus or minus 2.0. In the peptide compounds of this invention the ester, amide, disulfide or lanthionine linkage linking two amino acid residues is formed between the side chain functionalities. Thus, a amide linkage between the side chain carboxyl group of an acidic amino acid residue and the side chain amino group of a basic amino acid residue. Preferred acidic amino acid residues include: Asp, Glu, -NHCH [(CH2) 3CO2H] CO- and -NHCH [(CH2) 4CO2H] CO-, the most preferred of all Asp. Preferred basic amino acid residues include His, Lys, Orn, -NHCH (CH2NH2) CO- and -NHCH [(CH2) 2NH2] CO-, being Lys the most favorite of all. Ester ligatures are formed between the side chain carboxyl group of an acidic amino acid residue, such as those described above, and the side chain hydroxy group of an amino acid residue, such as Ser, Thr, Tyr and the like; Ser and Thr being especially preferred. Disulfides are formed from the amino acid residues containing side chain sulfhydryl groups. Cys is especially preferred for the formation of the disulfide bonds. Lathionine bridges are formed by desulfurization of the corresponding disulfide. The number of atoms in the bridge resulting from the amide, ester, disulfide or lanthionine bond formed as described above, will vary depending on the length of the side chain and the type of ligation (i.e., amide, ester, disulfide or lanthionine) ). The bridge preferably comprises from 4 to 12 atoms, more preferably from 6 to 10 atoms. A further preferred number of atoms contained in the bridge is 7; preferably comprising this bridge an amide ligature between the side chain functionalities of a Lys and an Asp residue.

A representative peptide compound of the present invention is denoted, for example, as cyclo (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2, with the amino acid residues linked within the parentheses, after "cycle" and the substituted amino acids of the natural sequence are placed in square brackets; hPTH represents human parathyroid hormone and hPTHrP, the protein related to human parathyroid hormone. The numbers within the second parenthesis refer to the number of amino acid residues present in the peptide compound, beginning at the end N (that is, the first 31 amino acids of hPTH). When the peptide compound of the present invention is substituted with a basic portion, acid addition salts are formed and are simply a more convenient use form; and in practice, the use of the salt form is inherently added to the use of the free base form. The acids which can be used to prepare the acid addition salts preferably include those which, when combined with the free base, produce pharmaceutically acceptable salts, ie salts whose anions are not toxic to the patient at the pharmaceutical doses of the salts, so that the beneficial effects inherent to the free base, due to collateral effects attributable to the anions, are not lost. While the pharmaceutically acceptable salts of said basic compounds are preferred, all acid addition salts are useful as sources of the free base form, even if the particular salt, per se, is suitable only as an intermediate product, for example, when salt is formed only for purposes of purification and identification, or when used as an intermediary in the preparation of a pharmaceutically acceptable salt by ion exchange processes. The pharmaceutically acceptable salts within the scope of the invention are those which are derived from the following acids: mineral acids, such as hydrochloric acid, sulfuric acid, phosphoric acid and sulfamic acid; and organic acids, such as acetic acid, citric acid, lactic acid, tartaric acid, malonic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, cyclohexylsulfamic acid, quinic acid and the like. The corresponding acid addition salts include the following: halogenhydrates, for example, hydrochloride and hydrobromide, sulfate, phosphate, nitrate, sulfamate, acetate, citrate, lactate, tartrate, malonate, oxalate, salicylate, propionate, succinate, fumarate, maieate, methylene-bis-β-hydroxynaphthates, gentisatos, mesylates, isethionates and di-p-toluoyltartrates , methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclohexyl sulfamate and quinate, respectively. According to another aspect of the invention, the acid addition salts of the peptide compounds of this invention are prepared by reaction of the free base with the appropriate acid, by application or adaptation of known methods. For example, the acid addition salts of the peptide compounds of this invention are prepared either by dissolving the free base in an aqueous or aqueous-alcoholic solution or in other suitable solvents containing the appropriate acid, and isolating the salt by evaporation of the solution, or by reacting the free base and ei acid in an organic solvent, in which case the salt is separated directly or can be obtained by concentration of the solution. Preferred acid addition salts are: trifluoroacetate, acetate and hydrochloride. Acetate and tetrahydrochloride salts are especially preferred. The peptide compounds of this invention can be regenerated from the salts by applying or adapting known methods.

For example, the original peptide compounds of the invention can be regenerated from their acid addition salts by treatment with an alkali, for example, an aqueous solution of sodium bicarbonate or an aqueous solution of ammonia. When the peptide compound of the invention is substituted with an acidic portion, base addition salts can be formed and are simply a more convenient use form; and in practice, the use of the salt form is inherently added to the use of the free acid form. The bases that can be used to prepare the base addition salts preferably include those which, when combined with the free acid, produce pharmaceutically acceptable salts, ie, salts whose cations are not toxic to an animal organism at pharmaceutically acceptable doses. of the salts, so that the beneficial effects inherent to the free acid, are not affected by collateral effects attributable to the cations. Pharmaceutically acceptable salts, including, for example, the alkali metal and alkaline earth metal salts, within the scope of the invention, are the derivatives of the following bases: sodium hydride, sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, ammonia, trimethylammonia, triethylammonia, ethylenediamine, n- methyl-glucamine, lysine, arginine, ornithine, choline, N, N'-dibenzylethylenediamine, chloroprocaine, diethanolamine, procaine, n-benzylphenethylamine, diethylamine, piperazine, tris (hydroxymethyl) -aminomethane, tetramethylammonium hydroxide and the like. The metal salts of the peptide compounds of the present invention can be obtained by contacting a hydride, hydroxide, carbonate or similar reactive compound of the selected metal, in an aqueous or organic solvent, with the free acid form of the peptide compound. The aqueous solvent employed may be water or may be a mixture of water with an organic solvent, preferably an alcohol, such as methanol or ethanol, a ketone such as acetone, an aliphatic ether, such as tetrahydrofuran, or an ester such as acetate of ethyl. Said reactions are usually carried out at room temperature but, if desired, they can be carried out with heating. The amine salts of the peptide compounds of the present invention can be obtained by contacting an amine in an aqueous or organic solvent with the free acid form of the peptide compound. Suitable aqueous solvents include water and mixtures of water with alcohols, such as methanol or ethanol, ethers such as tetrahydrofuran, nitriles such as acetonitrile or ketones, such as acetone. The amino acid salts can be prepared in a similar manner. The base addition salts of the peptide compounds of this invention can be regenerated from the salts by the application or adaptation of known methods. For example, the peptide compounds of the present invention can be regenerated from the base addition salts by treating them with an acid, for example, hydrochloric acid. In addition to being useful in themselves as active compounds, the salts of the peptide compounds of the invention are useful for the purification purposes of peptide compounds, for example, by exploiting the differences in solubility between the salts and the peptide compounds. originals, collateral products and / or starting materials, by techniques well known to those skilled in the art. "Pharmaceutically acceptable ester" means esters that will hydrolyze live and include those that decompose readily in the human body to leave the original peptide compound or a salt thereof. Suitable ester groups include, for example, pharmaceutically acceptable aliphatic carboxylic acid derivatives, particularly alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, wherein each alkyl or alkenyl portion advantageously has no more than six carbon atoms. The examples of esters Particular include: formates, acetates, propionates, butyrates, acrylates and ethylsuccinates. "Prodrug" means a compound that is rapidly transformed in vivo to produce the original peptide compound, for example, by hydrolysis in the blood. "Pharmaceutically acceptable prodrug" means a compound which, within the scope of sound medical judgment, is suitable for pharmaceutical use in a patient, without undue toxicity, irritation, allergic response and the like, and which is effective for the intended use, including a pharmaceutically acceptable ester, as well as a hybrid ion form, when possible, of the peptide compounds of the invention. The pharmaceutically acceptable prodrugs according to the invention are described in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, volume 14 of the ACS Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, both incorporated herein by this reference. "Solvate" means a physical association of a compound of this invention with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent binding, including the formation of hydrogen bonds. In some cases, the solvate will be capable of being isolated, for example, when one or more solvent molecules are incorporated into the crystalline lattice of the crystalline solid. "Solvate" covers both solvates in the solution phase and insulables. Representative solvates include ethanolates, methanolates and the like. "Hydrate" is a solvate in which the molecule or solvent molecules is / are H2O. The peptide compounds of the present invention may contain asymmetric centers in addition to the chiral centers in the backbone of the peptide compound. These asymmetric centers may be independently in any of the R or S configurations. It will be apparent to those skilled in the art that certain peptide compounds of the formula I may also exhibit geometric isomerism. Geometric isomers include the cis and trans forms of the peptide compounds of the invention, which have alkenyl portions. The present invention comprises geometric isomers and individual stereoisomers and mixtures thereof. These isomers can be separated from their mixtures, by application or adaptation of known methods, for example, by chromatographic techniques and recrystallization techniques, or they can be prepared separately from the appropriate isomers or their intermediates, for example, by application or adaptation of the methods described here.

THE PREFERRED MODALITIES Peptide compounds contemplated within the scope of the present invention include, but are not limited to: Cichium (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 3) [A1, Nle8, K18D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 4) cycle (K18-D22) [A1,2, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 5) -31) NH2 (SEQ ID NO: 6) (SEQ ID NO: 7), 18 P.22M-? 1.5 M. "8? X18 r.22, 27- cycle (K10-D ^) [A, '5, Nle0, K10, D ^, L¿ /] hPTH (1- 31) NH2 (SEQ ID NO: 8) (SEQ ID NO: 9) .18 r »22? R? 1.7 N? S? X18 r.22, 27-cycle (Kpo-D ^) [A '' ', Nle0, Klo, D ^, L ^] hPTH (1-31 ) NH2 (SEQ ID NO: 10) -31) NH2 (SEQ ID NO: 11) circle (K .1? 8o- ID-.2 ^ 2 \) G [A? 1 ',' 1l0u, Nle0, Klo, D ^, L ''] hPTH (1-31) NH2 (SEQ ID NO: 12) cycle (K18-D22) [A1'11, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 13) cycle (K18-D22) [A1'12, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 14) cycle (K18-D22) [A1'13, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 5) N22XG? 1.14 MI? 8? 18 n22, 27-cycle (K1ß-D ^) [Alll4, NleBfKlB, D ^, L ''] hPTH (1-31) NH2 (SEQ ID NO: 6), 18 G.22M-? 1.15 MO8? X18 n22 , 27-cycle (K1B-D ^) [A1'13lNleß, K? H, D? ILi £ /] hPTH (1-31) NH2 (SEQ ID NO: 7) (SEQ ID NO: 18), 18 n22xr? 1,17 M.O81 18 n22 i 27- cycle (K1b-D ^) [A1'1 /, NIe0, Kpo, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 19) -31) NH2 (SEQ ID NO: twenty) -31) NH2 (SEQ ID NO: 21) -31) NH2 (SEQ ID NO: 22), 18 r.22xr? 1 r? MI? 8? X18 n22. 2 cycle (K1B-D ^) [Al, G4, Nle °, Klo, D ^, L ''] hPTH (1-31) NH2 (SEQ ID NO: 23) ) NH2 (SEQ ID NO: 24) ) NH2 (SEQ ID NO: 25) cycle (K18-D22) [A1, G7, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K8-D22) [A1, G8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 27) cycle (K18-D22) [A1, G9, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18'-D22) [A1, G10, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18-D22) [A1, G11, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18-D22) [A1, G13, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18-D22) [A1, G14, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18-D22) [A1, G15, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18-D22) [A1, G16, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18-D22) [A1, G17, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18-D22) [D-P1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: cycle (K18-D22) [A1, D-P3, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID cycle (K18-D22) [A1, D-P6, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID O: 38), 18 G 22SG? r > or MI "8 IX18 n22, 27- c¡cio (KlB-D ^) [A \ D-P \ NleB, Klo, D ^ L ^ hPTH (1-31) NH2 (SEQ ID O: 39) (SEQ ID O: 40), 18 r.22 r? 1 r. o10 MI? 8 IX18 r > 22, 27-cyclo (K? B-D ^) [Al, D-P ?, NleO, Klo, D ^, L ^] hPTH (1-31) NH2 (SEQ ID O: 41) NO: 42) (SEQ ID NO: 43) (SEQ ID NO: 44) NO: 45), 18 r.22? 1 MI? 8? X18 r.22, 2 cycle (K1B-D ^) [A?, NleB, K? B, D ^, L ^] hPTH (1-34) NH2 (SEQ ID NO: 46) -31) NH2 (SEQ ID NO: 47) (SEQ ID NO: 48) cycle (D18-022) [A1, NIe8, D18, O22, L27] hPTH (1-31) NH2 (SEQ ID NO: 9) cycle (K1B-E22) [A \ NleB, K1B, EL ^] hPTH (1 -31) NH2 (SEQ ID NO: 0) (SEQ ID NO: 1) cycle (K1B-D ^) [A \ NleB, K1B, D ^ L ^] hPTH (1-30) NH2 (SEQ ID NO: 52) (SEQ ID NO: 53) C h (K1B-D ^) [A \ NleB, K1B, D L ^] hPTH (1-28) NH2 (SEQ ID NO: 54) cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-27) NH2 (SEQ ID NO: 55) acid (K18-D22) [K18, D22, L27] hPTH (10-31) NH2 (SEQ ID NO: 56) cycle (K18-D22) [K18, D22, L27] hPTH (9-31) NH2 ( SEQ ID NO: 57) cycle (K18-D22) [Nle8, K18, D22, L27] hPTH (8-31) NH2 (SEQ ID NO: 58) cycle (K18-D22) [Nle8, K18, D2, L27] hPTH (7-31) NH2 (SEQ ID NO: 59) cycle (K18-D22) [Nle8, K18, D22, L27] hPTH (6-31) NH2 (SEQ ID NO: 60) cyclo (K18-D22) [ Nle8, K18, D22, L27] hPTH (5-31) NH2 (SEQ ID NO: 61) cicio (K18-D22) [Nle8, K18, D22, L27] hPTH (4-31) NH2 (SEQ ID NO: 62 ) cicio (K18-D22) [Nle8, K18, D22, L27] hPTH (3-31) NH2 (SEQ ID NO: 63) cycle (K18-D22) [Nle8, K18, D22, L27] hPTH (2-31) ) NH2 (SEQ ID NO: 64) cycle (K10-D1) [A1, Nle8'18, K10, D14, L27] hPTH (1-31) NH2 (SEQ ID NO: 66) (SEQ ID NO: 67) ) NH2 (SEQ ID NO: 68) (SEQ ID NO: 69) (SEQ ID NO: 70) cycle (K18-D22) [K18, D22] hPTHrP (1-34) NH2 (SEQ ID NO: 71) cycle (K18-D22) [K18l26'30, D22, L23'28-31, E25'29] hPTH rP (1 -34) N H2 (SEQ ID NO: 72) bicyclo (K13-D17, K18-D22) [A1, Nle8, D17'22, K18, L27] hPTH (1-31) NH2 (SEQ ID NO: 73) bicyclo (K18-D22, K26-D30) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 74) bicyclo (K13-D17, K18- D22) [A1, Nle8, D17'22, K18, D22, L27] hPTH (1-34) NH2 (SEQ ID NO: 75) cycle (K18-D22) [K18, D22] hPTHrP (7-34) NH2 ( SEQ ID NO: 77) bicyclo (K13-D17, K18-D22) [Nle8, K, D17'22, L27] hPTH (7-34) NH2 (SEQ ID NO: 78) Cycle (K18-D22, K26-D30) [Nle8, K18, D22, L27] hPTH (7-34) NH2 (SEQ ID NO: 79) tricyclo (K13-D17, K18-D22, K26-D30) [A1, Nle8, K18, D17'22, L27] hPTH (1-31) NH2 (SEQ ID NO: 80) or a salt or prodrug thereof, pharmaceutically acceptable. A preferred cyclic peptide compound of formula 2 has the above formula, wherein the bridge formed from the side chains of a pair of amino acid residues is non-overlapping with a bridge formed between the side chains of another pair of residues. of amino acid. A more preferred cyclic peptide compound of formula 3 has formula 2 above, wherein A10 is Ala, Asn, Asp, Gly or Lys; A13 is Ala, Gly or Lys; Au is Ala, Asp, Gly, His, Lys or Ser; Ai7 is Ala, Asp, Gly, Lys or Be; Ais is Asp, Leu, Lys, Orn or Nie; A2? is Arg, Asp, Lys or Val; A22 is Asp, Glu, Lys, Orn or Phe; A25 is Arg, Asp, Glu, His or Lys; A26 is His or Lys; A29 is Ala, Asp, Glu or Gln; A3o is Asp, Glu or Lys; and The side chains of at least one of the following pairs of amino acid residues: A? 0 and Au, Ai3 and A? 7, Au, and A? 8, A? 7, and A2? Ais and A22, A2? and A25, A25 and A29 and A26 and A30, are linked by means of an amide bond to form a bridge, and the side chain of each of the following amino acid residues: A? 0, A13, Au, A? 7, A? 8, A2 ?, A22, A25, A2ß, A2g and A30 contribute, at most, to the formation of an individual and non-overlapping bridge; on condition that: (a) when the side chains of the pair of amino acid residues A13 and A? 7 are linked by means of an amide bond to form a bridge, then the side chains of at least one of the pairs of amino acid residues, A18 and A22, A2? and A25 and A2s and A2g are also linked by means of an amide ligature to form a bridge; (b) when the side chains of the next pair of amino acid residues: A26 and A30 are linked by means of an amide bond to form a bridge, then the side chains of at least one of the following pairs of amino acid residues A10 and Au, Au and A? 8, A17 and A2 ?, A? 8 and A22 and A2i and A25 are also linked by means of an amide bond to form a bridge; Y (c) when the side chains of the following pairs of amino acid residues: A 3 and A? and A26 and A30 are linked by means of an amide bond to form a bridge, then the side chains of one of the following pairs of amino acid residues A? 8 and A22 and A2? and A25 are also linked by means of an amide ligature to form a bridge. Another more preferred cyclic peptide compound of the formula 4 has the formula 3 above, where R a is H and Y is NH 2. Some cyclic peptide compounds of this invention possess agonistic activity on the parathyroid hormone receptor and, consequently, are useful in the treatment of physiological conditions associated with the regulation of calcium in bone cells, including hypocalcemia, osteoporosis, osteopenia and disorders associated with osteoporosis and osteopenia, such as: hyperparathyroidism, hypoparathyroidism and Cushings syndrome; glucocorticoid-induced osteopenia and immunosuppressant-induced; and repair of fracture and bone refracture. A preferred cyclic peptide agonist compound, of formula 5, has formula 4 above, wherein X is: (a) Ria-A? -A2-A3-A4-A5-A6-A7-A8-A9-; (b) R1a-A2-A3-A4-A5-A6-A7-A8-A9; or A more preferred cyclic peptide agonist compound of formula 6 has the formula 5 above, wherein Ai is Ala, Gly or D-Pro; A8 is Nie and A27 is Leu. Another, more preferred, cyclic peptide agonist compound of formula 7 has the formula 6 above, wherein: (i) the side chains of A10 and Au are linked by means of an amide bond, to form a bridge; (ii) the side chains of Au and A? 8 are linked by means of an amide bond, to form a bridge; (iii) the side chains of A and A2? they are linked by means of an amide ligature to form a bridge; (iv) the side chains of Ais and A22 are linked by means of an amide ligature to form a bridge; (v) the side chains of A2? and A25 are linked by means of an amide ligature to form a bridge; or (vi) the side chains of A25 and A29 are linked by means of an amide ligature to form a bridge. Another, more preferred, cyclic peptide agonist compound has the formula (i) above, wherein A10 is Asp or Lys; A13 is Lys; Au is Asp or Lys; A 7 is Asp or Ser; A18 is Nie; A2? is Arg or Val; A22 is Glu or Phe; A25 is Arg or His; A26 is Lys or His; A29 is Ala or Gln; and A30 is Asp or Glu; and the side chains of A10 and Au are linked by means of an amide ligature, to form a bridge. Another preferred form of cyclic peptide agonist compound has the formula (ii) above, wherein A10 is Asn or Asp; A13 is Lys; Au is Asp or Lys; TO? is Asp or Ser; A? 8 is Nie; A2? is Arg or Val; A22 is Glu or Phe; A25 is Arg or His; A26 is His or Lys; A29 is Ala or Gln; and A30 is Asp or Glu; and the side chains of A1 and Ais are linked by means of an amide ligature to form a bridge. Another more preferred cyclic peptide agonist compound has the formula (iii) above, wherein A 0 is Asn or Asp; A 3 is Lys; Au is His or Be; A? 7 is Asp or Lys; A 8 is Nie; A2? is Asp or Lys; A22 is Glu or Phe; A25 is Arg or His; A26 is His or Lys; A29 is Ala or Gln; and A30 is Asp or Glu; and the chains laterals of A? 7 and A21 are linked by means of an amide ligature to form a bridge. Another, more preferred cyclic peptide agonist compound has the formula (iv) above, wherein A10 is Asn or Asp; A13 is Lys, Au is His or Ser, A? 7 is Asp or Ser, A? 8 is Asp, Lis or Orn, A2? is Arg or Val, A22 is Asp, Glu, Lys or Orn, A25 is Arg or His, A26 is His or Lys, A29 is Ala or Gln and A30 is Asp or Glu; and the side chains of Aβ8 and A22 are linked by means of an amide ligature to form a bridge. Another, more preferred, cyclic peptide agonist compound has the formula (v) above, wherein A10 is Asn or Asp, A13 is Lys, Au is His or Ser, A? 7 is Asp or Ser, A? 8 is Nie, A21 is Asp or Lys, A22 is Glu or Phe, A25 is Asp or Lys, A26 is His or Lys, A2g is Ala or Gln and A30 is Asp or Glu; and the side chains of A2? and A25 are linked by means of an amide ligature to form a bridge. Another more preferred cyclic peptide agonist compound has the formula (vi) above, wherein A10 is Asn or Asp, A13 is Lys, Au is His or Ser, A? 7 is Asp or Ser, A? 8 is Nie, A2 is Arg or Val, A22 is Glu or Phe, A25 is Asp or Lys, A26 is His or Lys, A2g is Asp or Lys and A3o is Asp or Glu; and the side chains of A25 and A2g are linked by means of an amide ligature to form a bridge. Another, more preferred, cyclic peptide agonist of formula 8, has the formula 6 above, wherein: (vii) the side chains of A13 and A are linked by means of an amide bond and the side chains of A? 8 and A22 are linked by means of an amide bond to form a bridge; or (viii) the side chains of A? 8 and A22 are linked by means of an amide bond and the side chains of A26 and A30 are linked by means of an amide bond to form a bridge. Another more preferred cyclic peptide agonist compound has the formula (vii) above, wherein A10 is Asn or Asp, A13 is Lys or Asp, Au is His or Ser, A? 7 is Lys or Asp, Ais is Lys or Asp, A21 is Val or Arg, A22 is Glu, Lys or Asp, A25 is Arg or His, A26 is His or Lys, A2g is Ala or Gln and A30 is Asp or Glu; and the side chains of A13 and A? 7 are linked by means of an amide bond and the side chains of A? 8 and A22 are linked by means of an amide bond to form a bridge. Another cyclic peptide agonist compound, more preferred, has the formula (viii) above, in which A 0 is Asn or Asp, A13 is Lys, Au is His or Ser, TO? is Ser or Asp, A 8 is Lys or Asp, A2? is Val or Arg, A22 is Glu, Lys or Asp, A25 is Arg or His, A2ß is Lys or Asp, A29 is Ala or Gln and A30 is Lys or Asp, and the side chains of A? 8 and A22 are linked by means of an amide ligature and the side chains of A26 and A30 they are linked by means of an amide ligature to form a bridge. Another, more preferred cyclic peptide agonist of formula 9, has the formula 6 above, wherein the side chains of A13 and A? 7 are linked by means of an amide bond, and the side chains of Ais and A22 are linked by means of an amide bond, and the side chains of A26 and A30 are linked by means of an amide bond to form a bridge. Another, more preferred, cyclic peptide agonist of formula 10 has the formula 9 above in which A10 is Asn or Asp; A13 is Lys or Asp, Au is His or Ser, A? is Lys or Asp, A? 8 is Lys or Asp, A2? is Val or Arg, A22 is Glu, Lys or Asp, A25 is Arg or His, A26 is Lys or Asp, A29 is Ala or Gln and A30 is Lys or Asp. The most preferred cyclic peptide agonist compounds of this invention include: Cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 3) 'cycle (K18-D22) [A1'2, Nle8, K8, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 5) (SEQ ID NO: 6) cycle (K18-D22) [A1'4INle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 7) cycle (K18-D22) [A1'5, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 8) cycle (K18-D22) [A1'6, Nled, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 9) cycle (K18-D22) [A1'7, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 0) cycle (K1B-D ^) [A1'9, NleB, K? B , D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 1), 18 n22xr? 1.10 NM? 8 LX18 22, 27 cycle (K1B-D ^) [Ap '??, NleB, K1B, D ^, L¿ /] hPTH (1-31) NH2 (SEQ ID NO: 12), 18 G_22VGA1,11 MI "81X18 r« 22 i 2 cycle (K1B-D ^) [Ap '", Nle0, K, B, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO : 13) -31) NH2 (SEQ ID NO: 14), 18 G_22XG? 1.13 MI? 81X18 n22.27- cyclo (K1B-D ^) [Al '? D, NleB, KIB, D ^, L ^] hPTH (1- 31) NH2 (SEQ ID NO: ) .18 r.22? R? 1,14 |? 81x18 r.22, 27-cycle (KpB-D ^) [A, l4, NleB, Klo, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 16), 18 r.22? L, 15 M, "8? X18 r.22, 27-cycle (Kl ° -D ^) [Al'lo, Nle °, Klo, D ^, L¿ '] hPTH ( 1-31) NH2 (SEQ ID NO: 17) (SEQ ID NO: 18) -31) NH2 (SEQ ID NO: 19) (SEQ ID NO: twenty) (SEQ ID NO: 21) -31) NH2 (SEQ ID NO: 22) cycle (K1B-D ^) [Ap, G4, NleB, K1B, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 23) (SEQ ID NO: 24) (SEQ ID NO: 25) cycle (K18-D22) [A1, G7, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 26) cycle (K18-D22) [A1, G8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 27) cyclo (K18-D22) [A1, G9, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 28) cycle (K18-D22) [A1, G10, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 29) cycle (K18-D22) [A1, G11, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 30) 20 cycle (K8-D22) [A1, G13, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 31) cycle (K18-D22) [A1, G14, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 32) cycle (K18-D22) [A, G15, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 33) NO: 34) -31) NH2 (SEQ ID NO: 35), 18 r > 22 r. r > 1 M ?? 8, x18 n22, 27 cycle (KlB-D ^) [D-Pl, Nle °, KIB, D ^, L '] hPTH (1-31) NH2 (SEQ ID NO: 36), 18 r.22? R? 1 r > t_j3 I? 8 IX18 r.22, 27 cycle (KpB-D ^) [A \ D-P ^ NIeB, Klo, D L '] hPTH (1-31) NH2 (SEQ ID NO: 37), 18 r.22-? 1 r. D6 I? 8, X18 r > 22, 27-cycle (K1B-D ^) [A1, D-P °, Nle0, K'B, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 38) NO: 39), 18 r? 22xr? 1 r. D9 MI "8 IX18 ^ 22. 27 15 cycle (K1B-D ^) [A \ D-Pa, NleB, K? B, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 40) -SIJNHz (SEQ ID NO: 41) NO: 42), 18 r.22-? 1 r. ? 15 MI "8? X18 rv22, 27-cycle (KlB-D ^) [A?, D-Ppo, NleB, K1B, D ?, L ^] hPTH (1-31) NH2 (SEQ ID NO: 43) cycle (K18-D22) [A1, D-P16, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 44) (SEQ ID NO: 45) (SEQ ID NO: 46) (SEQ ID NO: 47) ) NH2 (SEQ ID NO: 48) ) NH2 (SEQ ID NO: 49) ) NH2 (SEQ ID NO: 50) cycle (OlB-E ^) [Al, NleB, 01B, E ^) L ^] hPTH (1-31) NH2 (SEQ ID NO: 51) (SEQ ID NO: 52) (SEQ ID NO: 53) C h (K1B-D ^) [A \ NleB, K1B, D L ^] hPTH (1-28) NH2 (SEQ ID NO: 54) cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-27) NH2 (SEQ ID NO: 5) cycle (K18-D22) [Nle8, K18, D22, L27] hPTH (3- 31) NH2 (SEQ ID NO: 63) cycle (K18-D22) [Nle8, K18, D22, L27] hPTH (2-31) NH2 (SEQ ID NO: 64) cycle (K10-D14) [A1, Nle8 ' 18, K10, D14) L27] hPTH (1-31) NH2 (SEQ ID NO: 6) cycle (K14-D18) [A1, Nle8, K14, D18, L27] hPTH (1-31) NH2 (SEQ ID NO. : 67) cycle (K17-D21) [A1, Nle8'18, K17, D21, L27] hPTH (1-31) NH2 (SEQ ID NO: 68) cycle (K21-D25) [A1, Nle8 '8, K21, D25, L27] hPTH (1-31) NH2 (SEQ ID NO: 69) cycle (K25-D29) [A1, Nle8'18, K25, D29, L27] hPTH (1-31) NH2 (SEQ ID NO: 70) cycle (K18-D22) [K18, D22] hPTHrP (1-34) NH2 (SEQ ID NO: 71) cycle (K18-D22) [K18'26'30, D22, L23.28'31, E25, 29] hPTHrP (1 -34) NH2 (SEQ ID NO: 72) bicycles (K13-D17, K18-D22) [A1, Nle8, D17'22, K18, L27] hPTH (1-31) NH2 (SEQ ID NO: 73) bicycles (K18-D22, K26-D30) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 74) tricycle (K13-D17, K18-D22, K26-D30) [A1, Nle8, K18, D17-22, L27] hPTH (1-31) NH2 (SEQ ID NO: 80) or a pharmaceutically acceptable salt or prodrug thereof. The even more preferred cyclic peptide agonist compounds of this invention include: Cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 3) (SEQ ID NO: 46), 18 r > 22xr? 1.3 M.? 81x18 r.22, 27- cycle (K1B-D ^) [Al'á, NleB, KlB, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 6 ), 18 r22 Nr? 1.6 M. 81x18 n22.27- cycloiK ^ -D ^ tA '^. NIe ^ K ^ .D ^ .L ^ jhPTHÍl-S NHz (SEQ ID NO: 9), 18_n22 r? 1.10 M, O8? X18 n22, 27 cycle (KpB-D ^) [A, '' u, Nle0, K, 0, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 12) -31) NH2 (SEQ ID NO: 13) -31) NH2 (SEQ ID NO: 14) '8_G. 2? 1,13 NMO8, X18 n22, 27- cycloid K-D ^ tA '-' ^ NIe ^ K ^ .D ^ .L ^ jhPTHÍl-S NHs (SEQ ID NO: 15) .18 rv22M-? 1, 14 MI? 8 IX18 n22, 27 cycle (K1B-D ^) [A? ? 4, NleB, KpB, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 16) cycle (K18-D22) [A1'15, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO:) (SEQ ID NO:) (SEQ ID NO:) cycle (K18-D22) [G1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO:) -31) NH2 (SEQ ID: 21) -31) NH2 (SEQ ID: 22) -31) NH2 (SEQ ID: 29) : 31) cycle (K1B-D '") [AlfG1> NleBfK1B, D ^, L' '] hPTH (1-31) NH2' (SEQ ID: 34) -31) NH2 (SEQ ID: 35), 18 r, 22 rrv d I "8 IX18 rv22, 27-cycle (K1B-D ^) [DP \ NleB, K1B, DL¿ '] hPTH (1-31) NH2 (SEQ ID NO:) cycle (D18-K22) [A1, Nle8, D18, K22, L27] hPTH (1-31) NH2 (SEQ ID NO: 7) -31) NH2 (SEQ ID NO: 8) ) NH2 (SEQ ID NO: 9) -31) NH2 (SEQ ID NO: fifty) (SEQ ID NO: 51) (SEQ ID NO: 52), 18 rv22-? 1 Ml 8? X18 v22, 27- c.clo (K1B-D ^) [A \ Nle0, KIB, D L ^] hPTH (1-29) NH2 (SEQ ID NO: 53) 54) (SEQ ID NO: 66) cyCl (K14-D18) [A1, Nle8, K14, D18, L27] hPTH (1-31) NH2 (SEQ ID NO: 67) ) NH2 (SEQ ID NO: 68) cycle (K21-D25) [A1, Nle8'18, K21, D25, L27] hPTH (1-31) NH2 (SEQ ID NO: 9) cycle (K25-D29) [A1, NIe8'18, K25, D29, L27] hPTH (1-31) NH2 (SEQ ID NO: 70) cycle (K18-D22) [K18, D22] hPTHrP (1-34) NH2 (SEQ ID NO: 71) cycle (K18-D22) [K18'26'30, D22, L23'28-31, E25 ' 29] hPTHrP (1-34) NH2 (SEQ ID NO: 72) bicyclo (K13-D17, K18-D22) [A1, Nle8, D17'22, K18, L27] hPTH (1-31) NH2 (SEQ ID NO. : 73) bicycles (K18-D22, K26-D30) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 74) tricyclo (K13-D17, K18-D22, K26-D30) [A1, Nle8, K18, D17'22, L27] hPTH (1-31) NH2 (SEQ ID NO: 80) or a salt or pharmaceutically acceptable prodrug thereof. Even more preferred cyclic peptide agonist compounds include: Cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 3) (SEQ ID NO: 46) (SEQ ID NO: 12) (SEQ ID NO: 4), 18 rv22sr? 1.13 MI? 8 IX18 rv22, 27-cycle (KlB-D ^) [A1'IJ, Nle0, Klo, D ^, L] hPTH (1-31) NH2 (SEQ ID NO: 5), 18 rv22 r? 1.14. "8, x18 G 22, 27- cycloid K ^ -D ^ A '^. NIe ^ K ^ .D ^ .L ^ jhPTHÍl-SIJNHs (SEQ ID DO NOT: 16) (SEQ ID NO: 18) '18_n22 r? 1.17 M | O8, x18 n22, 27-cycle (KlB-D ^) [Al'l /, Nle °, Klo, D ^, L ^] hPTH (1-31) NH2 ( SEQ ID NO: 19) -31) NH2 (SEQ ID NO: 22), 18 rv22? L r13 MI? 8 IX-18 rv22, 27-cycle (K1B-D ^) [A ', GIJ, Nle0, KIB, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 31) cycle (K18-D22) [A1, G16, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 34) .18 G 22U-? 1 r1 MI .-. 8 IX18 rv22.27 cycle (KIB-D ^) [Al, G ", NIeB, KIB, D ^, L ^] hPTH (1-31) NH2 (SEQ ID NO: 35) cycle (K18-D22) [D-P1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 36) cycle (D18-K22) [A1, Nle8, D18, K22, L27] hPTH (1-31) NH2 (SEQ ID NO: 47) cycle (K18-E22) [A1, Nle8, K18, E22, L27] hPTH (1-31) NH2 (SEQ ID NO: 0) cycle (018-E22) [A1, Nle8.018, E22, L27] hPTH ( 1-31) NH2 (SEQ ID NO: 1) cyclo (K18-D22) [A, NIe8, K8, D22, L27] hPTH (1-30) NH2 (SEQ ID NO: 52) cycle (K14-D18) [A1, Nle8, K14, D18, L27] hPTH (1-31) NH2 (SEQ ID NO: 67) cycle (K18-D22) [K18, D22] hPTHrP (1-34) NH2 (SEQ ID NO: 71) bicyclo (K13-D17, K18-D22) [A1, Nle8, D17'22, K18, L27] hPTH (1-31) NH2 (SEQ ID NO: 73) bicyclo (K18-D22, K26-D30) [A1, Nle8, K8, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 74) tricycle (K13-D17, K18 -D22, K26-D30) [A1, Nle8, K18, D17'22, L27] hPTH (1-31) NH2 (SEQ ID NO: 80) or a pharmaceutically acceptable salt or prodrug thereof. Another cyclic peptide agonist compound still much more preferred is bicyclo (K13-D17, K26-D30) [A1, Nle8'18, D17, L27] hPTH (1-31) NH2 (SEQ ID NO: 79), or a salt or prodrug thereof, pharmaceutically acceptable. Some cyclic peptide compounds of this invention inhibit the action of PTH. Said cyclic peptide antagonist compounds are useful in the treatment of disorders characterized by a excess of PTH, such as hyperparathyroidism and hypercalcemia crisis related to hyperparathyroidism, malignant hypercalcemia, renal failure and hypertension. A preferred cyclic peptide antagonist compound, of formula 10, has the formula 6 above, wherein X is: (a) R a-A4-A5-A6-A7-A8-Ag-, (b) R a -A5-A6-A7-A8-A9-, (c) Ria-A6-A7-A8-A9-, (d) Ria-A7-A8-A9-, (f) Rib-A9-, and A more preferred cyclic peptide antagonist compound of formula 11 has formula 10 above, wherein A8 is Nie and A27 is Leu. Another more preferred cyclic peptide antagonist compound of formula 12 has the formula 1 above, in which the side chains of Aβ8 and A22 are linked by means of an amide ligature to form a bridge. Another most preferred cyclic peptide antagonist compound of formula 13 has formula 12 above, wherein A 0 is Asn or Asp, A 13 is Lys, A is His or Ser, A 7 is Asp or Ser, A 8 is Asp, Lys or Orn, A2? is Arg or Val, A22 is Asp, Glu, Lys or Orn, A25 is Arg or His, A26 is His or Lys, A29 is Ala or Gln and A3o is Asp or Glu.

More preferred cyclic peptide antagonist compounds include: cyclo (K18-D22) [K18, D22, L27] hPTH (10-31) NH2 (SEQ ID NO: 56) cycle (K18-D22) [K18, D22, L27] hPTH (9-31) NH2 (SEQ ID NO: 57) Cycle (K18-D22) [Nle8, K18, D22, L27] hPTH (8-31) NH2 (SEQ ID NO: 58) Cycle (K18-D22) [Nle8 , K18, D22, L27] hPTH (7-31) NH2 (SEQ ID NO: 59) cycle (K18-D22) [Nle8, K18, D22, L27] hPTH (6-31) NH2 (SEQ ID NO: 60) Cyclo (K18-D22) [Nle8, K18, D22, L27] hPTH (5-31) NH2 (SEQ ID NO: 61) Cycle (K18-D22) [Nle8, K18, D22, L27] hPTH (4-31) NH2 (SEQ ID NO: 62) cycle (K18-D22) [Nle8, K8, D22, L27] hPTH (7-34) NH2 (SEQ ID NO: 65) and cycle (K18-D22) [K18, D22] hPTHrP (7-34) NH2 (SEQ ID NO: 77) or a pharmaceutically acceptable salt or prodrug thereof. Some acyclic peptide compounds of this invention also possess agonist activity on the parathyroid hormone receptor and, consequently, are useful in the treatment of physiological conditions associated with the regulation of calcium in bone cells, including hypocalcemia, osteoporosis, osteopenia and disorders associated with osteoporosis and osteopenia, such as hyperparathyroidism, hypoparathyroidism and Cushings syndrome; Osteopenia induced by glucocorticoids and by immunosuppressants, and repair of fractures and bone refractures. A preferred acyclic peptide agonist compound, of the formula 14, is a peptide compound of formula II, wherein R? A is H and Y is NH2.

A more preferred acyclic peptide agonist compound, of formula 15, has formula 14 above, wherein X is: (a) Ria-A1-A2-A3, A4-A5-A6-A7-A8-A9-, ( b) Ria-A2-A3-A4-A5-A6-A7-A8-A9-, or (c) R a-A3-A4-A5-A6-A7-A8-A9-. Another, more preferred, acyclic peptide agonist of formula 16 has the formula 15 above, wherein A is Ser, Ala, Gly or D-Pro; A2 is Ala, Val or Gly; A3 is Ala, Ser, Gly or D-Pro; A4 is Glu, Ala or Gly; A5 is He, His, Ala or Gly; A6 is Ala, Gln, Gly or D-Pro, A7 is Ala, Leu, Gly; A8 is Leu, Nie, Gly or D-Pro, Ag is His, Ala, Gly or D-Pro; A10 is Ala, Asn, Gly, Asp or D-Pro, An is Ala, Gly, Leu or Lys, A? 2 is Ala or Gly, A13 is Ala, Gly or Lys, A is Ala, Gly, His, Ser or D-Pro, A15 is Ala, Gly, He or D-Pro, A? 6 is Asn, Ala, Gly, D-Pro or Gln, A? 7 is Ala, Asp, Gly, Ser or D-Pro, A? 8 is Lys, A? 9 is Arg or Glu, A20 is Arg, A21 is Arg or Val, A22 is Asp, Lys, Orn or Glu, A23 is Leu, Phe or Trp, A24 is Leu, A25 is Arg or His, A26 is Lys or His, A27 is Leu or Lys, A28 is He or Leu, or an equivalent amino acid thereof; A2g is Ala or Gln, A30 is Asp or Glu, A31 is Lie, Leu or Val, A32 is His, A33 is Asn or Thr and A34 is Ala or Phe. Another most preferred acyclic peptide agonist compound of formula 17 has the formula 16 above, wherein Ai is Ala, Gly or D-Pro, A8 is Nie, A22 is Asp and A27 is Leu. Another most preferred acyclic peptide agonist compound of formula 18 has formula 17 above, wherein X is A7-A8-A9-.

An even more preferred acyclic peptide agonist compound is [A1, Nle8, K18, D22, L27) hPTH (1-3) NH2 (SEQ ID NO: 4) or a pharmaceutically acceptable salt or prodrug thereof. It should be undeod that this invention covers all appropriate combinations of the preferred aspects of the invention, to which reference is made herein.

SYNTHESIS OF PEPTIDE COMPOUNDS The peptide compounds of the present invention can be synthesized by any techniques that are known to those skilled in the field of peptide synthesis. For a synthesis of solid phase peptides, a summary of the many techniques can be found in JM Stewart and JD Young, Solid Phase Peptide Synthesis, WH Freeman Co. (San Francisco), 1963, and J. Meienhofer, Hormonal Proteins and Peptides , Volume 2, page 46, Academic Press (New York), 1973. For a classic synthesis in solution, see G. Schroder and K. Lupke, The Peptides, Volume 1, Academic Press (New York), 1965. In general, these methods comprise the sequential addition of one or more amino acids or suitably protected amino acids to a growing peptide chain. Normally the amino or carboxyl group of the first amino acid is protected by a suitable protecting group. The amino acid protected or formed derivative, can be fixed to a support solid inert, or used in solution, adding the next amino acid of the sequence, having the complementary group (amino or carboxyl) suitably protected, under suitable conditions to form the amide ligature. The protecting group is then removed from the newly added amino acid residue and the next amino acid (suitably protected) is then added, and so on. After all the desired amino acids have been linked in the proper sequence, any remaining protecting groups (and any solid support) are removed, sequentially or concurrently, to give the final peptide compound. By simple modification of this general procedure, it is possible to add more than one amino acid at a time, to a growing chain, for example, by coupling (under conditions that do not racemize the chiral centers) a tripeptide protected with an appropriately protected dipeptide, to form , after removing the protection, a pentapeptide, and so on. A preferred method for preparing the peptide compounds of the present invention involves the synthesis of the peptide in solid phase. In this particularly preferred method, the alpha-amino function is protected by means of an acid-sensitive or base-sensitive group. Said protective groups must have the property of being stable to the conditions of formation of the peptide binding and at the same time of being easily eliminated without destruction of the growing peptide chain or racemization of any of the chiral centers contained therein. Suitable protecting groups are: 9-fluorenylmethyloxycarbonyl (Fmoc), terbutyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), biphenylisopropyloxycarbonyl, teramyloxycarbonyl, isobornyloxycarbonyl, (alpha, alpha) dimethyl-3,5-dimethoxybenzyloxycarbonyl, o-nitrophenylsulfenyl, 2-cyano-tert-butyloxycarbonyl and the like. The protecting group 9-fluorenylmethyloxycarbonyl (Fmoc) is preferred. Particularly preferred side chain protecting groups are, for the side chain amino groups, as in lysine and arginine: 2,2,5,7,8-pentamethylchroman-6-sulphonyl (pmc), nitro, p-toluenesulfonyl, -methoxybenzenesulfonyl, Cbz, Boc, AIloc (allyloxycarbonyl) and adamantyloxycarbonyl; for tyrosine: benzyl, o-bromobenzyloxycarbonyl, 2,6-dichlorobenzyl, isopropyl, tertbutyl (t-Bu), cyclohexyl, cyclopentyl and acetyl (Ac); for serine: terbutyl, benzyl and tetrahydropyranyl; for histidine: tritiio, benzyl, Cbz, p-toluenesulfonyl and 2,5-dinitrophenyl; for tryptophan: formyl and Boc; for asparagine and glutamine: Trt (tritiio), for aspartic acid and glutamic acid: O-t-Bu and O-allyl. The cyclic peptide compounds of the present invention are preferably prepared using a fragment-based approach, wherein a fragment of the desired complete peptide compound, containing the amide, ester, disulfide or lanthionine bridge (the cyclic peptide fragment) it is prepared separately and purified before coupling it to an amino acid or peptide portion, bound by resin, of the complete peptide compound. The cyclic peptide fragment is prepared using classical techniques of solution phase synthesis or solid phase peptide synthesis methodology, as described herein. The synthesis of the complete peptide compound is achieved then by sequential addition of the remaining amino acid residues to the resin bound cyclic peptide; by adding other cyclic or acyclic peptide fragments to the resin-bound cyclic peptide; or by any combination of the above. The preparation of the cyclic peptide hPTH analogs, using a fragment-based approach, is described in U.S. Patent Application Serial No. 60/081897, filed April 15, 1998, incorporated herein by this reference. The peptides of this invention, wherein R? C is: are prepared using the method described by R. Waelchli and co-authors, Tetrahedron Lett., 6 (10), 1151-1156 (1996), incorporated herein by this reference. The following non-limiting examples will serve to further illustrate the preparation of the novel peptides of this invention.

GENERAL METHODS The peptide compounds are prepared in a PS3 synthesizer of peptides in solid phase, automatic, from Protein Technologies, Inc., using the methodology for solid phase peptide synthesis (SPPS (acronym for its designation in English: Solid-Phase Peptide Synthesis). with Fmoc, common and current, Acquired amino acids protected with Fmoc from Advanced ChemTech (Louisville, KY, USA), Bachem (Torrance, CA, USA) or Senn Chemicals AG (Dielsdorf, Switzerland), and appear in the following list: Fmoc-Ala-OH, Fmoc-Arg (Pmc-OH, Fmoc-Asn (Trt) -OH, Fmoc-Asp (OtBu) -OH, Fmoc-Asp (Oalyl), Fmoc-Cys (Acm) -OH, Fmoc-Cys (Trt-OH, Fmoc-Glu (OtBu) -Oh, Fmoc-Glu (Oalyl) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Gly-OH, Fmoc-His (Trt) -OH, Fmoc-lle-OH, Fmoc-Leu-OH, Fmoc-Lys (Alloc) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Orn (Alloc) -OH, Fmoc-Phe-OH, Fmoc-Ser (tBu) ) -OH, Fmoc-Thr (tBu) -OH, Fmoc-Trp (Boc) -OH and Fmoc-Val-OH. The amino acid analysis is carried out by BACHEM Bioscience, King of Prussia, PA, USA, and α reported as amino acid residue: value found (expected value). Sequence analysis is performed in the Microchemistry facilities of the Emory University School of Medicine, in Atlanta, GA, E. U. A.

PREPARATION OF THE AMIDA BRIDGE The cyclic peptide compounds are prepared, with amide bridge, forming an amide linkage between the side chain carboxyl group of an acidic amino acid residue and the side chain amino group of a basic amino acid residue, in the presence of an activating agent such as described above. Preferred acidic amino acid residues include: Asp, Glu, -NHCH [(CH2) 3C02H] CO- and -NHCH [(CH2) 4C02H] CO-, with Asp being most preferred. Preferred basic amino acid residues include: His, Lys, Orn, -NHCH (CH2NH2) CO- and -NHCH [(CH2) 2NH2] CO-, Lys being most preferred. In cases where the peptide precursor for the cyclic peptide compound contains more than one acidic or basic amino acid residue, protective groups for additional acidic or basic amino acids are selected, so that the amino acids to be cyclized can be selectively unprotected. Preferably, the desired acidic and basic amino acid residues are simultaneously deprotected. Additionally, in addition to being stable to the reagents used to deprotect the basic amino acid residues and selected acids, the protecting groups in the remaining amino acid residues are selected to be stable to the cyclization conditions employed.

The term "orthogonality", when used in reference to side chain protecting groups, refers to a situation as described herein, in which there are two or more classes of protecting groups in a molecule; each class being optimally eliminated under specific conditions, while remaining stable to the conditions used to eliminate the protective groups in other classes. Thus, all protective groups of one class can be eliminated, while all others are left intact. Preferred protecting groups having the desired orthogonality are: for the acidic acid residue to be cyclized: allyl; for the basic amino acid residue to be cyclized: allyloxycarbonyl (alloc); for any additional acidic amino acid residues: terbutyl (tBu); and for any additional basic amino acid residues: terbutyloxycarbonyl (Boc). The allyl and allyloxycarbonyl protecting groups are simultaneously removed by treatment with palladium, preferably tetracis (triphenylphosphine) palladium (0). The formation of the amide bridge is then achieved as described herein for the formation of the amide ligature.

PREPARATION OF THE ESTER BRIDGE The cyclic peptide compounds with ester bridging are prepared by the formation of an ester ligation between the carboxyl group of side chain of an acidic amino acid residue and the side chain hydroxyl group of an amino acid residue containing hydroxyl. Preferred acidic amino acid residues include Asp, Glu, -NHCH [(CH2) 3CO2 H] CO- and -NHCH [(CH2) 4C02H] CO-, with Asp being most preferred. Preferred amino acid residues containing a side chain hydroxyl group include Ser, Thr, Tyr and the like, with Ser and Thr being especially preferred. The formation of the ester ligation is achieved using the methods and reagents described above for the formation of an amide bridge.

PREPARATION OF THE DISULFIDE BRIDGE The cyclic peptide compounds with disulfide bridge are prepared by the formation of a disulfide bond between the amino acid residues containing side chain sulfhydryl groups, of which Cys is especially preferred. Preferred protecting groups for the side chain sulfhydryl residues are trityl (Trt) and acetamidomethyl (Acm). The treatment of the fully protected peptide precursor, the cyclic peptide compound with disulfide bridge, with an oxidizing agent, for example, thallium trifluoroacetate rri (CF3CO2) 3_ in dimethylformamide (DMF) effects the selective removal of the protective group Trt or Acm and the formation concomitant disulfide ligature.

PREPARATION OF THE LANTIONINA BRIDGE The lanthionine-based variants of the disulphide bridge analogs described above are prepared from the disulfide using the desulfurization method described by Harp and Gleason (J. Org. Chem., 1971, 36, 73-80). After the oxidative removal of Cys (Trt) or Cys (Acm) [or homocys derivatives] and disulfide bridge formation, the peptide is treated with tris (diethylamine) phosphine in an appropriate solvent. After the recommended washings, the remaining side chain protective groups are removed, as described above. The crude peptide compound is then purified using reverse phase liquid chromatography.

EXAMPLE 1 Ala-Val-Ser-GIu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu, Leu-Gln-Asp-Val amide METHOD A 0.75 g (0.41 mmol) of MBHA amide resin Rink (Nova Biochem, La Jolla, CA, E. U. A.) is charged in a reaction vessel and swelled for 10 minutes using 10 ml of DMF. Then the N-terminal Fmoc protective group, for 5 minutes, using 15 ml of a 20% piperidine solution in DMF. The resin is washed six times with 15 ml of DMF and then treated for 20 minutes with a solution containing 0. 34 g (1.0 mmol) of Fmoc-Val-OH and 0.38 g (1.0 mmol) of HBTU in 5 ml of 0.4 M of N-methylmorpholine (NMM) / DMF. After the first amino acid coupling, the resin is washed three times with 15 ml of DMF. The deprotection / coupling procedure is repeated using the following amino acid residues: Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalyl) -OH, Fmoc Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH and Fmoc-Lys (Alloc) -OH. The resin-bound peptide is then separated from the instrument and washed five times with 50 ml of DMF, five times with 50 ml of THF and five times with 50 ml of diethyl ether. After drying in the air, the resin is suspended under a nitrogen atmosphere in 40 ml of chloroform / acetic acid / NMM, 37: 2: 1. 2.8 g (2.4 mmol) of tetracis (triphenylphosphine) palladium (0) is added and the heterogeneous mixture is stirred moderately for two hours at room temperature. The resulting homogeneous solution is filtered and the resin is successively washed with 100 ml of 0.5% diisopropylethylamine / DMF, 100 ml of sodium diethyldithiocarbonate / 0.5% DMF and 200 ml of DMF. The cyclization between the side chains of Lys18 and Asp22 is carried out within two hours, using 0.26 g (0.62 mmol) of HBTU, 0.08 g (0.62 mmol) of HOBT and 0.14 ml (1.23 mmol) of NMM in 20 ml of DMF anhydrous; then the step of cyclization for the second time. The solvent is removed and the resin is successively washed with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether and air dried. A portion of 0.46 g (approximately 0.1 mmol) of this peptide bound to the resin is returned to the automatic synthesizer and the remaining seventeen amino acid residues are added, as previously described, in the following order: Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH; Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc -Ala-OH The N-terminal Fmoc protecting group is removed within 5 minutes using 15 ml of a 20% piperidine / DMF solution. The resin-bound peptide is removed from the instrument and washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 10 ml of TFA containing 0.5 ml of water, 0.5 ml of thioanisole, 0.75 g of phenol and 0.25 ml of ethanedithiol. After two hours the TFA solution is filtered in 60 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The resin is washed with 2 ml of TFA that is added to the peptide mixture. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 30 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 50 ml of 0.1% TFA and lyophilized to dryness.

The crude peptide is purified by high performance liquid chromatography, in reverse phase, using a Rainin HPLC system, equipped with a DYNAMAX-60A C18 column, of 2.54 cm. The mobile phase starts with water (0.1% TFA) and is raced for 30 minutes until 60% ACN (0.08% TFA) / water (0.1% TFA). The pure fractions eluting at approximately 23 minutes are combined and lyophilized to give 40 mg of the purified peptide. IS-MS: 3634 (M +). Amino acid analysis: Asp / Asn: 3.86 (4); Ser: 1.85 (2), Glu / Gln: 4.00 (4), Gly: 0.98 (1), Ala: 0.97 (1); Val 2.86 (3); He: 0.95 (1), Leu: 6.49 (6), Nie: 0.91 (1), Lys: 2.75 (3), His: 2.06 (2), Arg: 2.09 (2), Trp: not determined (1). The position of the amide bridge is confirmed by Edman degradation and by map formation by tryptic digestion.

METHOD B 0.75 g (0.41 mmol) of MBHA amide resin Rink (Nova Biochem, La Jolla, CA, E. U.A.) is charged in a reaction vessel and swelled for 10 minutes using 10 ml of DMF. The N-terminal Fmoc protecting group is then removed, for 5 minutes, using a 17 ml solution of 20% piperidine in DMF. The resin is washed six times with 17 ml of DMF and then treated for 20 minutes with a solution containing 0.34 g (1.0 mmol) of Fmoc-Val-OH and 0.38 g (1.0 mmol) of HBTU in 8 ml of 0.4 M. of N- methylmorpholine (NMM) / DMF. After the first amino acid coupling, the resin is washed three times with 17 ml of DMF. The deprotection / coupling procedure is repeated using the following amino acid residues: Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) ) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (OaliI) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) - OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu-OH. The peptide bound to the resin is then removed from the instrument and washed five times with 50 ml of DMF, five times with 50 ml of THF and five times with 5 ml of diethyl ether. After drying in the air, the resin is suspended under a nitrogen atmosphere in 40 ml of chloroform / acetic acid / NMM 37: 2: 1. 1.0 g (0.86 mmol) of tetracis (triphenylphosphine) palladium (0) is added and the heterogeneous mixture is stirred moderately for two hours at room temperature. The resulting homogeneous solution is filtered and the resin is successively washed with 100 ml of 0.5% diisopropylethylamine "/ DMF, 100 ml of 0.5% sodium diethyldithiocarbonate / DMF and 200 ml of DMF.The cyclization between the side chains of Lys18 and Asp22 is carried out for two hours using 0.23 g (0.62 mmol) of HBTU, 0.08 g (0.62 mmol) of HOBT and 0.13 ml (1.23 mmol) of NMM in 20 ml of anhydrous DMF.; then the cycling step is performed a second time. The solvent is removed and the resin is successively washed with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and air dried.

Approximately 2.2 g of the peptide bound to the resin is returned to the automatic synthesizer and the remaining fourteen amino acid residues are added, as previously described, in the order: Fmoc-His (Trt) -OH, F-moc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) ) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. The N-terminal Fmoc protecting group is removed for five minutes using 17 ml of 20% piperidine / DMF solution. The peptide bound to the resin is removed from the instrument and washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The resin is washed with 2 ml of TFA, which is added to the peptide mixture. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. The washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. The crude peptide is purified by reverse phase liquid chromatography, as previously described to give 261 mg of the sample material, in mass spectral and HPLC analysis, to be identical to an authentic sample, prepared by method A. In addition , the material provided by method B is identical to that prepared by method A, in the in vitro analysis, in the analysis of ROS cell cAMP 17.2 / 8 (see above).

METHOD C 0.75 g (0.41 mmol) of Rink amide is charged with MBHA resin (Nova Biochem, La Jolla, CA, E. U. A.), in a reaction vessel and swelled for 10 minutes using 10 ml of DMF. The N-terminal Fmoc protecting group is then removed for 5 minutes using 17 ml of a 20% piperidine solution in DMF. The resin is washed six times with 17 ml of DMF and then treated for 20 minutes with a solution containing 0.34 g (1.0 mmol) of Fmoc-Val-OH and 0.38 g (1.0 mmol) of HBTU in 8 ml of 0.4 M of N-methylmorpholine (NMM) / DMF. After the coupling of the first amino acid, the resin is washed three times with 17 ml of DMF. The deprotection / coupling procedure is repeated using the following amino acid residues: Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) ) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmol-Val-OH, Fmoc-Arg (Pmc) - OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH; Fmoc- Asn (Trt) -OH, Fmoc-Leu-OH; Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Gln (Trt) -OH, FmoI-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc Ser (tBu) = - OH, Fmoc-Val-OH and Fmoc-Ala-OH. Then the bound peptide is removed to the resin of the instrument and washed five times with 50 ml of DMF, five times with 50 ml of THF and five times with 50 ml of diethyl ether. After drying in the air, the resin is suspended under a nitrogen atmosphere in 40 ml of a 37: 2: 1 solution of chloroform / acetic acid / NMM. 1.0 g (0.86 mmol) of tetracis (triphenylphosphine) palladium (0) is added and the heterogeneous mixture is stirred moderately for two hours at room temperature. The resulting homogeneous solution is filtered and the resin washed successively with 100 ml of 0.5% diisopropylethyleneimine / DMF, 100 ml of 0.5% sodium diethyldithiocarbonate / DMF and 200 ml of DMF. Cyclization is performed between the side chains of Lys18 and Asp22 for two hours using 0.23 g (0.62 mmol) of HBTU, 0.08 g (0.62 mmol) of HOBT and 0.13 ml (1.23 mmol) of NMM in 20 ml of anhydrous DMF; and then the cyclization step is carried out for the second time. The solvent is removed and the resin is washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and air-dried. The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. The resin-bound peptide is washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of terbutylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The resin is washed with 2 ml of TFA that is added to the peptide mixture. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted.

The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. The washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. The crude peptide is purified by reverse phase liquid chromatography, as previously described to provide purified peptide, which shows, by mass spectral analysis and HPLC, that it is identical to authentic samples prepared by methods A and B. In addition, the material provided by method C is identical to that prepared by methods A and B in the in vitro analysis and in the cAMP analysis of ROS cell 17.2 / 8 (see above).

METHOD D Here incorporated by reference is the fragment-based synthesis of the title compound, which is described in US Patent Application Serial No. 60/081897, filed on April 15, 1998.

EXAMPLE 2 rA1, Nle8, K18P22, L27.hPTH (1-31) NH? (SEQ ID NO: 4) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser-Lys-Glu-Arg-Val-Asp-Trp-Leu-Arg- Lys-Leu-Leu-GIn-Asp-Val amide 0.75 g (0.41 mmol) of Rink amide and MBHA resin (Nova Biochem, La Jolla, CA, USA) are loaded into a reaction vessel and swelled for 10 minutes using 10 ml of DMF. The N-terminal Fmoc protecting group is then removed for 5 minutes, using a 17 ml solution of 20% piperidine in DMF. The resin is washed six times with 17 ml of DMF and then treated for 20 minutes with a solution containing 0.34 g (1.0 mmol) of Fmoc-Val-OH and 0.38 g (1.0 mmol) of HBTU in 8 ml of 0.4 M. of N-methylmorpholine (NMM) / DMF. After the coupling of the first amino acid, the resin is washed three times with 17 ml of DMF. The deprotection / coupling procedure is repeated using the following amino acid residues: Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) ) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) - OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (AIIoc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-G! U (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH . Then the instrument is removed peptide bound to the resin and washed five times with 50 ml of DMF, five times with 50 ml of THF and five times with 50 ml of diethyl ether. After drying in air, a portion of 1.5 g (about 0.25 mmol) of the resin is suspended, under a nitrogen atmosphere, in 20 ml of a 37: 2: 1 solution of chloroform / acetic acid / NMM. 0.5 g (0.43 mmol) of tetracis (triphenylphosphine) palladium (0) is added and the heterogeneous mixture is stirred moderately for two hours at room temperature. The resulting homogeneous solution is filtered and the resin washed successively with 100 ml of 0.5% diisopropylethylamine / DMF, 200 ml of 0.5% sodium diethyldithiocarbonate / DMF, 200 ml of DMF, 100 ml of THF, 100 ml of diethyl ether , and it dries in the air. The N-terminal Fmoc protecting group is removed for 5 minutes using 20 ml of a 20% piperidine / DMF solution. The peptide bound to the resin is successively washed with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 20 ml of TFA containing 1.0 ml of water, 1.0 ml of thioanisole, 1.5 g of phenol and 0.5 ml of ethanedithiol. After 2 hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The resin is washed with 2 ml of TFA that is added to the peptide mixture. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This procedure is repeated four times and dried vacuum the resulting peptide, dissolved in 100 ml of water containing 0. 1% TFA and lyophilized to dryness. The crude peptide is purified by reverse phase liquid chromatography as previously described, to provide 75 mg of final purified peptide. IS-MS 3652 (M +). Amino acid analysis: Asp / Asn: 4.00 (4); Ser: 1.78 (2), Glu / Gln 3. 92 (4); Gly: 0.95 (1), Wing 0.95 (1), Val, 3.03 (3); lie, 0.90 (1); Leu, 6.36 (6); Nie, 0.90 (1); Lys, 3.06 (3); His, 2.01 (2); Arg, 2.04 (2); Trp: not determined (1). The primary sequence of the peptide is confirmed by degradation of Edman EXAMPLES 3-18 A 0.46 g portion is distributed evenly (around 0. 1 mmol) of the resin-bound peptide, prepared previously using method A, and ending with the amide bridge between K18-D22, between 17 concavities of three milliliters, of a block of 96 concavities, of an Advanced ChemTech 496 MBS instrument. In each concavity the N-terminal Fmoc protecting group is removed using 0.5 ml of a 20% piperidine / DMF solution. A synthesis program is used that allows the independent preparation of all seventeen PTH analogs in which L-alanine is systematically substituted, in each of the seventeen N-terminal positions, using normal coupling conditions with F-moc (0.5 mmol of Fmoc-amino acid per coupling step, triple couplings per residue). After the scheduled synthesis is complete, the PTH analogs are deprotected and removed from the resin using reagent K (1.0 ml / concavity) for a period of two hours. The release solutions are then individually added to 8 ml of diethyl ether, at room temperature. The resulting heterogeneous mixtures of the peptide precipitated in diethyl ether are then centrifuged and the supernatant of the crude peptides is decanted off. The solid peptides are successively washed with five 8 ml portions of diethyl ether, followed by vacuum drying. Dissolve the white solids in 2 ml of water containing 0.1% TFA and lyophilize. The peptides are weighed, analyzed by ion spray mass spectrometry and their ability to stimulate the formation of cAMP in ROS cells 17.2 / 8 is analyzed using the method described (see below).

EXAMPLE 3 Cycle (K18-D22) rA1 2, Nle8, K1ß, D22, L271hPTH (1-31) NH? (SEQ ID NO: 5) Ala-AIa-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-GIn-Asp-Val amide. IS-MS = 3605 (M +).

EXAMPLE 4, 18 rv > 2? R? 1.3 M, "8, 18" 22, 27- C0CIO (K -P '"_ GA1 NIeB.K ™ P ^" lhPT? (1-31) NHa (SEQ ID NO: 6) Ala-Val-Ala-Glu-lle-Gln-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. IS-MS = 3617 (M +).

EXAMPLE 5 Cycle (K18D22) rA1 4, Nle8, K18.D22, L271hPTH (1-31) NH? (SEQ ID NO: 7) Ala-Val-Ser-Ala-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-GIn-Asp-Val amide. IS-MS = 3575 (M +).

EXAMPLE 6 Ala-Val-Ser-Glu-Ala-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. IS-MS = 3591 (M +).

EXAMPLE 7 CYCLE (K18-D22) GA1 -6, Nle8, K18, D22, L271hPTH (1-31) NH? (SEQ ID NO: 9) Ala-Val-Ser-Glu-lle-Aia-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3576 (M +).

EXAMPLE 8 CYCLE (K18-D22) GA1 7, Nle8, K18, D22, L27.hPTH (1-31) NH? (SEQ ID NO: 10) Ala-Val-Ser-Glu-lle-GIn-Ala-NIe-His-Asn-Leu-Giy-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3591 (M +).

EXAMPLE 9 Cycle (K18-D22) rA1 8.K18, D22.L271hPTH (1-31) NH? (SEQ ID NO: 81) Ala-Val-Ser-Glu-lle-GIn-Leu-Ala-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-GlnAsp-Val amide. IS-MS = 3591 (M +).

EXAMPLE 10 CYCLE (K 8-D22) GA1 9, Nle8.K18.D22, L271hPTH (1-31) NH? (SEQ ID NO: 11) Ala-Val-Ser-Giu-lle-GIn-Leu-Nle-Ala-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. IS-MS = 3567 (M +).

EXAMPLE 11 CYCLE (K18-P22) GA1 -10, Nle8, Ki8, D22, L271hPTH (1-31 .NH? (SEQ ID NO: 12) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Ala-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3590 (M +).

EXAMPLE 12 Cycle (K1B-D ^) "A1, 11.NIeB.K1 .D '", Lz # hPTH (1-31) NH9 (SEQ ID NO: 13) Ala-Val-Ser-GIu-lle-GIn-Leu-Nle-His-Asn-Ala-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3591 (M +).

EXAMPLE 13 Cycle (K18-P22) rA 12.NIe8.K18, P22, L27) hPTH (1-31) NH7 (SEQ IP NO: 14) Ala-Val-Ser-Glu-lle-GIn-Leu-NIe-His-Asn-Leu-Ala-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3647 (M +).

EXAMPLE 14 CYCLE (K18-P22) GA1 13.NIe8, K18, P22.L271hPTH (1-31) NH? (SEQ IP NO: 15) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Ala-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3576 (M +).

EXAMPLE 15 Cycle (K? A-P ^) rA1 14.NIeB.K1B.P ^ .L; / 1hPTH (1-31) NH? (SEQ IP NO: 16) Ala-Val-Ser-GIu-lle, Gln-Leu-Nle-His-Asn-Leu-Gly-Lys-Ala-Leu-Asn-Ser- (Lys-GIu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-VaI amide. IS-MS = 3567 (M +).

EXAMPLE 16 r 8_n22? L.15 M. "8, x18 n22, 2 CÍCIO_KIB-P _ GA1? A, Nleg, K1B.P ^ .L ^ 1hPTH (1-31) -NH? (SEQ IP NO: 17) Ala-Val-Ser-Glu-Ile-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Ala-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3591 (M +).

EXAMPLE 17 Cycle (K18-P22) rA1 '16, Nle8, K18.P22, L27lhPTH (1-31) NH? (SEQ IP NO: 18) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-GIy-Lys-His-Leu-Ala-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3590 (M +).

EXAMPLE 18 Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ala- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3617 (M +).

EXAMPLES 19-34 A portion of the peptide bound to resin, previously prepared using method A, is distributed uniformly and ends with the amide bridge K18-D22 (0.46 g, about 0.1 mmol), between 17 concavities of 3 ml, of a block of 96 concavities, of an Advanced Chem Tech 496 MBS instrument. In each concavity the N-terminal Fmoc protecting group is separated using 0.5 ml of a 20% piperidine / DMF solution. A synthetic program is used that allows the independent preparation of the seventeen PTH analogues, where "glycine is systematically substituted in each of the seventeen N-terminal positions, using common Fmoc coupling conditions and currents (0.5 mmol F). -moc-amino acid per coupling step, triple bonds per residue.) After completing the programmed synthesis, the PTH analogs are deprotected and separated from the resin using reagent K (1.0 ml / concavity) for a period of two hours Then the diethyl ether division solutions are added individually at room temperature, the resulting heterogeneous mixtures of the precipitated peptide are then centrifuged in diethyl ether, and the supernatant of the crude peptides is decanted. solid peptides with five 8 ml portions of diethyl ether, followed by vacuum drying. s white in 2 ml of water containing 0.1% TFA, freeze and lyophilize.

The peptides are weighed, analyzed by mass spectrometry with ion spray, and their ability to stimulate the formation of cAMP in ROS 17.2 / 8 cells is analyzed, using the method described (see below).

EXAMPLE 19 Cycle (K18-D22) rG \ Nle8, K18, D22, L271hPTH (1-31) NH? (SEQ ID NO: 20) Gly-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. IS-MS = 3619 (M +).

EXAMPLE 20 Cycle (K18-D22) rA1, G2, Nle8, K18, D22, L271hPTH (1-31) NH9 (SEQ ID NO: 21) Ala-GIy-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. IS-MS = 3591 (M +).

EXAMPLE 21 Ala-Val-Gly-GIu-Ile-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-GIN-Asp-Val amide IS-MS = 3603 (M +).

EXAMPLE 22 Cycle (K18-D22) rA1, G4, Nle8, K18, D22, L271hPTH (1-31) -NH? (SEQ ID NO: 23) Ala-Val-Ser-Gly-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-GIu-Arg-VaI-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3561 (M +) EXAMPLE 23 Cycle (K1B-D ^) rA \ Ga, NleB, K1B, D ^, L HhPTH (1-31) NH? (SEQ ID NO: 24) Ala-Val-Ser-Glu-Gly-Gln-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3577 (M +).

EXAMPLE 24 Cycle (K1B-D ^) rA1, Gb.NIeB, K1B, D ^ L: hPTH (1-31) NH? (SEQ ID NO: 25) Ala-Val-Ser-Glu-lle-Gly-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gin-Asp-Val amide IS-MS = 3562 (M +) EXAMPLE 25 Cycle (K18-P22) rA1.G7.NIe8.K18.P22.L27lhPTH (1-31) NH? (SEQ IP NO: 26) Ala-Val-Ser-Glu-lle-GIn-Gly-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-GIn-Asp-Val amide IS-MS = 3577 (M +).

EXAMPLE 26 Cycle (K 8-P22) rA1, G8, K18, P22.L271hPTH (1-31) NH? (SEQ IP NO: 27) Ala-Val-Ser-Glu-lle-GIn-Leu-GIy-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-VaI-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3577 (M +).

EXAMPLE 27 cycle (K18-D22) rA1, G9, Nle8.K18.D22, L271 PTH (1-31) NH? (SEQ ID NO: 28) Ala-Val-Ser-Glu-lle-Gn-Leu-NIe-GIy-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3553 (M +) EXAMPLE 28 cycle (K18-D22) rA1, G10.NIe8, K18, D22, L27lhPTH (1-31) NH? (SEQ ID NO: 29) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Gly-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3576 (M +) EXAMPLE 29 cycle (K18-D22) rA1, G11, Nle8, K18, D22, L271hPTH (1-31) NH? (SEQ ID NO: 30) Ala-Val-Ser-Giu-lle-GIn-Leu-Nle-His-Asn-Gly-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3577 (M +) EXAMPLE 30 cycle (K1B-D ^) rA \ G1j, NleB, K1B, D ^, L; / 1hPTH (1-31) NHp (SEQ ID NO: 31) Ala-Val-Ser-GIu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Gly-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide - IS-MS = 3562 (M +).

EXAMPLE 31 cycle (K18-D22) rA1, G14.NIe8.K18.D22.L271hPTH (1-31) NH? (SEQ ID NO: 32) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-Gly-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3553 (M +) EXAMPLE 32 Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-GIy-Lys-His-Gly-Asn-Ser- (Lys-Glu-Arg-VaI-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3577 (M +) EXAMPLE 33 Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Gly-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3576 (M *) EXAMPLE 34 cycle (K18-D22) rA1, G17, Nle8.K18.D22.L271hPTH (1-31) NH? (SEQ IP NO: 35) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Gly- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3603 (M +) EXAMPLES 35-51 A portion of 0.46 g (about 0.1 mmol) of the resin-bound peptide, previously prepared using method A, is distributed evenly and ending with an amide bridge K18-D22, between 17 concavities of three ml, of a block of 96 concavities, of an Advanced Chem Tech 496 MBS instrument. In each concavity the N-terminal Fmoc protecting group is removed using 0.5 ml of 20% piperidine / DMF. A synthesis program is used that allows the independent preparation of the 17 PTH analogs, where D-proinin is systematically substituted at each of the 17 N-terminal positions, using common Fmoc coupling conditions and currents (0.5 mmol Fmoc-amino acid per coupling step), triple couplings per residue). After the programmed synthesis is complete, the PTH analogs are deprotected and separated from the resin using 1.0 ml / concavity of K reagent, for a period of two hours. The division solutions are then added individually to 8 ml of diethyl ether, at room temperature. The resulting heterogeneous mixtures of the peptide precipitated in diethyl ether are then centrifuged and the supernatant of the crude peptides decanted. The solid peptides are successively washed with five 8 ml portions of diethyl ether, followed by vacuum drying. White solids containing 0.1% TFA are dissolved in 2 ml of water, frozen and lyophilized. The peptides are weighed, analyzed by ion spray mass spectrometry and analyzed for their ability to stimulate the formation of cAMP in ROS 17.2 / 8 cells, using the method described (see below).

EXAMPLE 35 cycle (K18-D22) rD-P1, Nle8, K18, D22X271hPTH (1-31) NH9 (SEQ ID NO: 36) D-Pro-Val-Ser-GIu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3659 (M +).

EXAMPLE 36 Ala-D-Pro-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3631 (M +).

EXAMPLE 37 Ala-Val-D-Pro-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3643 (M +) EXAMPLE 38 Cycle (K1B-D ^). A \ D-P, NIe8, K1B, D¿, L 71hPTH (1-31) NH2 (SEQ ID NO: 83) Ala-Val-Ser-D-Pro-He-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3601 (M +).

EXAMPLE 39 Cyclo (K18-D22) rA1, D-P5.NIe8, K18, D22.L271hPTH (1-31) NH? (SEQ ID NO: 84) Ala-Val-Ser-Glu-D-Pro-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-GIu-Arg-VaI-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3617 (M +).

EXAMPLE 40 cycle (K18-D22) rAi, D-P6, Nle8, K18, D22, L271hPTH (1-31) NH9 (SEQ ID NO: 38) Ala-Val-Ser-Glu-lle-D-Pro-Leu-Nle-His-Asn-Leu-Giy-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-VaI-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-VaI amide IS-MS = 3602 (M +) EXAMPLE 41 Ala-Val-Ser-GIu-lle-GIn-D-Pro-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3617 (M +).

EXAMPLE 42 Ala-Val-Ser-Glu-lle-GIn-Leu-D-Pro-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-VaI-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3617 (M +).

EXAMPLE 43 Cyclo (K18-D22) rAi.P-P9, Nle8.K18.P22.L271hPTH (1-31) NH? (SEQ IP NO: 40) Ala-Val-Ser-Glu-Ile-GIn-Leu-Nle-D-Pro-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-GIu-Arg-VaI-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3593 (M +).

EXAMPLE 44 cycle (K18-D22) rA1.D-P10, Nleß.K18, P22.L271hPTH (1-31) NH? (SEQ IP NO: 41) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-D-Pro-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3616 (M +).

EXAMPLE 45 Cycle (K18-P22) rA1, D-P11, Nle8, K18, D22, L271hPTH (1-31) NH? (SEQ ID NO: 86) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-D-Pro-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3617 (M +).

EXAMPLE 46 Cycle (K18-D22) rA1, D-P12.NIe8.K18.D22, L271hPTH (1-31) N ^ (SEQ ID NO: 87) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-D-Pro-Lys-His-Leu-Asn-Ser- (Lys-GIu-Arg-VaI-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3673 (M +).

EXAMPLE 47 Cycle (K18-D22) rA1, D-P13-Nle8, K18.D22.L271hPTH (1-31) NH2 (SEQ ID NO: 88) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-D-Pro-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide. IS-MS = 3602 (M +) EXAMPLE 48 cycle (K1B-D ^). A \ P-P NleB, K P ~ L 71hPTH (1-31) NH? (SEQ IP NO: 42) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-D-Pro-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3593 (M +).

EXAMPLE 49 cycle (K18-D22) rA1.D-P15.NIe8, K18, D22, L271hPTH (1-31) NH? (SEQ ID NO: 43) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-D-Pro-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3617 (M +).

EXAMPLE 50 Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-D-Pro-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3616 (M +).

EXAMPLE 51 Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-D-Pro- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val amide IS-MS = 3643 (M +).

EXAMPLE 52 cycle (K1B-D ^) rA \ NleB, K? A, D ^ L? / LhPTH (1-34) NH2 (SEQ ID NO: 46) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-GIy-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val-His-Asn-Phe amide The peptide is prepared in a manner analogous to that previously described (Method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel, which is then fixed to an automatic Protein Technologies PS 3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with the SPMO with Fmoc base: Fmoc-Phe-OH, Fmoc-Asn (Trt) -OH, Fmoc His (Trt) - OH, Fmoc-Val-OH, Fmoc-Asp (OtBut) -OH, Fmoc-GIn (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) - OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH. Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (tBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu-OH. As previously described, the resin-bound peptide is then removed from the instrument for Pd-mediated side chain deprotection of the Lys (AIIoc) and Asp (Oalyl) residues and subsequent intramolecular cyclization of side chain to side chain. Following the described treatment procedures, the peptide bound to amide-containing resin is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc-OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) ) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc -Val-OH and Fmoc-Ala-OH The resin-bound peptide is removed from the instrument and the N-terminal Fmoc protecting group is removed for five minutes using 17 ml of 20% piperidine / DMF solution. resin-bound peptide with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 g of ethanedithiol After 2 hours, the TFA solution is filtered in 160 ml of tert-butyl ether at 0 ° C, which precipitates the crude peptide, centrifuges the peptide mixture at 2500 rpm for 5 minutes and The white solid is resuspended in 120 ml diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is dried under vacuum, it is dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. The crude peptide is then purified by reverse phase liquid chromatography to give 320 mg of the final purified peptide, as a white solid.

IS-MS: 4032 (M +). Amino acid analysis: Asp / Asn: 5.00 (5), Ser, 1.63 (2), Glu / Gln, 3.81 (4), Gly, 0. 90 (1), Wing, 0.85 (1), Val, 2.71 (3), lie, 0.84 (1), Leu, 6.35 (6), Nie, 0.77 (1), Phe, 1.07 (1), Lys, 2.90 (3), His, 2.80 (3), Arg, 1.96 (2), Trp: not determined d).

EXAMPLE 53 cycle (D18-K22) rA1.NIe8, P18.K22.L271hPTH (1-31) NH? (SEQ IP NO: 47) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Asp-Glu-Arg-Val-Lys) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide is placed with resin MBHA in a reaction vessel that is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH , Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH , Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc -Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then removed from the instrument for Pe-mediated side chain deprotection of the Lys (Alloc) and Asp (Oalyl) residues and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness.

The crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 252 mg of final purified peptide, as a white solid. IS-MS 3634 (M +). Amino acid analysis: Asp / Asn: 3.97 (4), Ser, 1.88 (2), Glu / Gln, 3.95 (4), Gly, 1.00 (1), Ala, 0.99 (1), Val, 2.91 (3), lie, 0.87 (1), Leu, 6.57 (6), Nie, 0.80 (1), Lys, 2.90 (3), His, 2.12 (2), Arg, 2.05 (2), Trp, not determined (1 ).

EXAMPLE 54 Ala-Val-Ser-Glu-IIe-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Om-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. . . The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Vai-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Orn (Alloc) -OH, Fmoc- Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then removed from the instrument for Pd-mediated side chain deprotection of the Orn (Alloc) and Asp (OaliIo) residues and the subsequent intramolecular cyclization of side chain to side chain. The protective group is removed N-terminal Fmoc for 5 minutes, using 17 ml of a 20% piperidine / DMF solution. The peptide bound resin is washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. The crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 251 mg of final purified peptide, as a white solid.

IS-MS: 3620 (M +). Amino acid analysis: Asp / Asn 4.00 (4), Ser, 1.76 (2), Glu / Gln, 3. 98 (4), Gly, 0.98 (1), Wing, 0.95 (1), Val, 2.94 (3), He, 0.88 (1), Leu, 6.52 (6), Nie, 0.84 (1), Lys, 2.03 (2), His, 194 (2), Arg, 2.01 (2), Trp, not determined (1).

EXAMPLE 55 Ala-Val-Ser-Glu-IIe-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Asp-Glu-Arg-VaI-0m) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Om (Alloc) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Asp (Oalil) -OH; Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc -Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As described previously, the peptide bound to resin for Pd-mediated side chain deprotection, Orn (Alloc) and Asp (Oalil), and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After 2 hours the solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. The crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 414 mg of final, purified peptide, as a white solid. IS-MS: 3620 (M +). Amino acid analysis: Asp / Asn, 4.00 (4), Ser, 181 (2), Glu / Gln, 3. 93 (4), Gly, 0.99 (1), Ala, 0.97 (1), Val, 2.67 (3), lie, 0.87 (1), Leu, 6.39 (6), Nie, 0.79 (1), Lys, 1.98 (2), His, 1.97 (2), Arg, 1.97 (2), Trp, not determined (1) - EXAMPLE 56 clcle (K 8-E22) rA1, Nleß.K18, E22.L271hPTH (1-31) NH? (SEQ ID NO: 50) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Glu) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val-amide The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol Rank amide with resin is placed MBHA in a reaction vessel that is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmol-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmol-Leu-OH, Fmoc-Leu OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Glu (Oail) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH , Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc -Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide of the instrument is then removed, for Pd-mediated side chain deprotection, from the Lys (Alloc) and Glu (Oalyl) residues and the subsequent intramolecular cyclization from side chain to side chain . The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. Wash successively the peptide bound to resin with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the solution is filtered in 160 ml of terbutylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. The crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 95 mg of final purified peptide, as a white solid. IS-MS: 3648 (M +). Amino acid analysis: Asp / Asn: 3.00 (3), Ser: 1.70 (2), Glu / Gln: 4.75 (5), Gly 0.93 (1); Wing, 0.89 (1), Val, 2.80 (3), He, 0.89 (1), Leu, 6.16 (6), Nie, 0.87 (1), Lys, 2.99 (3), His, 1.86 (2), Arg , 1.90 (2), Trp: not determined (1).

EXAMPLE 57 cycle (O18-E22) rA \ Nle8, O18, E22, L271hPTH (1-31) NH; > (SEQ ID NO: 51) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Orn-Glu-Arg-Val-Glu) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide is placed with resin MBHA in a reaction vessel that is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a consistent manner with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Glu (O-allyl) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Om (A! Ioc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc Leu-OH, Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) - OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val -OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Om (Alloc) and Glu (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes, using 17 ml of a 20% piperidine / DMF solution. Wash successively the peptide bound to resin with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide.

The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. The crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 237 mg of purified final peptide, as a white solid. IS-MS: 3634 (M +). Amino acid analysis: Asp / Asn: 3.09 (3), Ser, 1.74 (2), Glu / Gln, . 02 (5), Gly, 0.97 (1), Ala, 0.93 (1), Val, 2.95 (3), He, 0.88 (1), Leu, 6.44 (6), Nie, 0.85 (1), Lys, 2.06 (2), His, 1.89 (2), Arg, 1.98 (2), Trp: not determined (D- EXAMPLE 58 cycle (K18-D22) rA \ Nle8.K18, D22.L271hPTH (1 -30) NH2 (SEQ ID NO: 52) Ala-Val-Ser-GIu-lle-Gln-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp amide The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) ) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (AIIoc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His ( Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Giu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH . As previously described, the resin-bound peptide is then removed from the instrument for deprotection of the Pd-mediated side chain, from the Lys (Alloc) and Asp (Oaliio) residues, and subsequent intramolecular cyclization from side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes, using 17 ml of a 20% piperidine / DMF solution. The peptide is washed successively bound to resin with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether.

The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted.

This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. A portion of the crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 53 mg of final purified peptide as a white solid. IS-MS: 3534 (M +) Analysis of amino acid: Asp / Asn: 4.00 (4), Ser, 1.71 (2), Glu / Gln: 3. 89 (4), Gly, 0.93 (1), Wing: 0.92 (1), Val, 1.87 (2), He, 0.90 (1), Leu, 6.46 (6), Nie, 0.82 (1), Lys, 2.89 (3), His, 2.01 (2); Arg, 2.03 (2), Trp: not determined (1 )- EXAMPLE 59 cycle (K18-P22) rA1, Nle8, K18.D22.L271hPTH (1 -29) NH? (SEQ IP NO: 53) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-GIy-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu-Gln amide. The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp ( Oalil) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His- (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) - OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes, using 17 ml of a 20% piperidine / DMF solution. The resin-bound peptide is washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. Then a portion of the crude peptide is purified by reverse phase liquid chromatography, as previously described, to give 100 mg of final purified peptide, as a white solid. IS-MS: 3419 (M +). Amino acid analysis: Asp / Asn, 2.85 (3), Ser, 1.73 (2), Glu / Gln, 3. 98 (4), Gly, 1.00 (1), Wing, 0.98 (1), Val, 2.00 (2), He, 0.93 (1), Leu, 6.47 (6), Nie, 0.97 (1), Lys, 2.99 (3), His, 2.09 (2), Arg, 1.99 (2), Trp, not determined (1 )- EXAMPLE 60 cycle (K18-D22) rA1, Nle8.K18.D22, L271hPTH (1-28) NH? (SEQ ID NO: 54) Ala-Val-Ser-Glu-Ile-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu-Leu amide The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu -OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) ) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly- OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle -OH, Fmoc-GIu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes, using 17 ml of a 20% piperidine / DMF solution. The resin-bound peptide is washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. A portion of the crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 51 mg of the purified final peptide, as a white solid. IS-MS: 3291 (M +). Amino acid analysis: Asp / Asn: 2.81 (3), Ser, 1.71 (2), Glu / Gln: 2. 86 (3), Gly, 0.97 (1), Ala, 1.00 (1), Val, 1.93 (2), lie, 0.91 (1), Leu, 6.30 (6), Nie, 0.92 (1), Lys, 2.88 (3), His, 2.03 (2), Arg, 1.93 (2), Trp, not determined (1).

EXAMPLE 61 cycle (K18-D22) rA1.NIe8.K18.D22, L271hPTH (1 -27) NH? (SEQ ID NO: 55) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg-Lys-Leu amide. The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc-OH, Fmoc-Asp (Oa! Il) -OH, Fmoc-Val-OH, Fmoc-Arg (Pnpc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH , Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc -Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH As previously described, the resin-bound peptide is then removed from the instrument for deprotection of the Pd-mediated side chain, the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of lateral chain to side chain The N-terminal Fmoc protecting group is removed for 5 minutes, using 17 ml of a 20% piperidine / DMF solution, the resin-bound peptide is washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. Air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. A portion of the crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 65 mg of the purified final peptide, as a white solid. IS-MS: 3178 (M +). Amino acid analysis: Asp / Asn, 2.74 (3), Ser, 1.75 (2), Glu / Gln, 2.88 (3), Gly, 0.95 (1), Ala, 1 .00 (1), Val, 1 .94 (2), He, 0.93 (1), Leu, 5.16 (5), Nie, 0.88 (1), Lys, 2.84 (3), His, 2.01 (2), Arg, 1 .93 (2), Trp, undetermined (D- EXAMPLE 62 cycle (K1B-D) rK1B.D ^ L7-hPTH (10-31) NH? (SEQ ID NO: 56) Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-GIn-Asp-Val amide.

The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc-OH, Fmoc-Gly-OH, Fmoc-Leu-OH and Fmoc-Asn (Trt) -OH). about 50 mg portion of the resin-bound peptide, and the N-terminal Fmoc protecting group is removed for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. ml of DMF, 10 ml of THF and 10 ml of diethyl ether The air-dried resin is suspended in 2 ml of TFA containing water, thioanisole, phenol and ethanedithiol in the proportions described before. After two hours the TFA solution is filtered in 8 ml of tert-butyimethyl ether at 0 ° C, which effects the precipitation of the crude peptide.

The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 10 ml of 0.1% TFA and lyophilized to dryness. IS-MS: 2642 (M +).

EXAMPLE 63 His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg-Lys-Leu-Leu-GIn-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) ) -OH, Fmoc- Asn (Trt) -OH and Fmoc-Leu-OH. As previously described, it is removed then the resin-bound peptide of the instrument for deprotection of the side chain mediated by Pd, of the residues Lys (Alloc) and Asp (Oalilo), and subsequent intramolecular cyclization of side chain to side chain.

After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH and Fmoc-His ( Trt) -OH. A portion of about 50 mg of the resin-bound peptide is removed from the instrument, and the N-terminal Fmoc protecting group is removed for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 10 ml of DMF, 10 ml of THF and 10 ml of diethyl ether. The air-dried resin is suspended in 2 ml of TFA containing water, thioanisole, phenol and ethanedithiol in the proportions described above. After two hours the TFA solution is filtered in 8 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resultant peptide is vacuum dried, dissolved in water containing 10 ml of 0.1% TFA and lyophilized to dryness. IS-MS: 2780 (M +).

EXAMPLE 64 cycle (K18-D22) rNle8.K18.P22.L271hPTH (8-31) NH? (SEQ IP NO: 58) Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val Amide . The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oail) -OH, Fmoc-Val-OH , Fmoc-Arg- (Pmc) -OH, Fmoc-Glu (OtBu) -OH. Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His ( Trt) -OH and Fmoc-Nle-OH. A portion of the instrument is removed from the instrument about 50 mg of the peptide bound to resin, and the protective group is removed N-terminal Fmoc for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 10 ml of DMF, 10 ml of THF and 10 ml of diethyl ether. The air-dried resin is suspended in 2 ml of TFA containing water, thioanisole, phenol and ethanedithiol in the proportions described above. After two hours the TFA solution is filtered in 8 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 10 ml of 0.1% TFA and lyophilized to dryness. IS-MS: 2892 (M +).

EXAMPLE 65 c_clo (K .118g-rD_22v) rNleg, K, 118g, nD2 ~ 2, L 2¿7 / .hPTH (7-31) NH7 (SEQ ID NO: 59) Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg-Lys-Leu-Leu-Gln-Asp- Val amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. It is added sequentially the following amino acids in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH , Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His ( Trt) -OH, Fmoc-Nle-OH, and Fmoc-Leu-OH. A portion of about 50 mg of the resin-bound peptide is removed from the instrument, and the N-terminal Fmoc protecting group is removed for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 10 ml of DMF, 10 ml of THF and 10 ml of diethyl ether. The air-dried resin is suspended in 2 ml of TFA containing water, thioanisole, phenol and ethanedithiol in the proportions described above. After two hours the TFA solution is filtered in 8 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted.

The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 10 ml of TFA ai 0. 1% and lyophilized to dryness. IS-MS: 3006 (M +).

EXAMPLE 66 c (K18-D22) .Nle8, K18, D22, L27_hPTH (6-31) NH2 (SEQ ID NO: 60) Gln-Leu-Nle-His-Asn-Leu-GIy-Lys-His-Leu-Asn-Ser- (Lys-GIu-Arg-Val-Asp) -Trp-Leu-Arg-Lys-Leu-Leu-Gln- Asp-Val amide The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-GIn (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu OH. As previously described, the resin-bound peptide is then removed from the instrument for deprotection of the Pd-mediated side chain, the Lys (Alloc) and Asp (Oalyl) residues, and Subsequent intramolecular cyclization from side chain to side chain.

After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His ( Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH and Fmoc-Gln (Trt) -OH. A portion of about 50 mg of the resin-bound peptide is removed from the instrument, and the N-terminal Fmoc protecting group is removed for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. The resin-bound peptide is washed successively with 10 ml of DMF, 10 ml of THF and 10 ml of diethyl ether. The air-dried resin is suspended in 2 ml of TFA containing water, thioanisole, phenol and ethanedithiol in the proportions described above. After two hours the TFA solution is filtered in 8 ml of tert-butyimethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 10 ml of 0.1% TFA and lyophilized to dryness. IS-MS: 3135 (M +).

EXAMPLE 67 cycle (K1B-D ^) rNle .8B, .K, 118B, rD »2 ~ 2, L 27 / -1hPTH (5-31) NH? (SEQ ID NO: 61) lle-Gln-Leu-Nle-His-Asn-Leu-GIy-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg-Lys-Leu-Leu Gln-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu OH. As previously described, the resin bound peptide is then removed from the instrument for deprotection of the iaterai chain mediated by Pd, from the Lys (Alloc) and Asp (Oalilo) residues, and subsequent intramolecular cyclization from side chain to side chain. After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His ( Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH and Fmoc-lle-OH.

A portion of about 50 mg of the resin-bound peptide is removed from the instrument, and the N-terminal Fmoc protecting group is removed for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 10 ml of DMF, 10 ml of THF and 10 ml of diethyl ether. The air-dried resin is suspended in 2 ml of TFA containing water, thioanisole, phenol and ethanedithiol in the proportions described above. After two hours the TFA solution is filtered in 8 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 10 ml of 0.1% TFA and lyophilized to dryness. IS-MS: 3247 (M +).

EXAMPLE 68 c.clo (K1B-D) rNle .8s,? Kx118B. rD »2¿2 IL 2z7 / .hPTH (4-31) NH, (SEQ ID NO: 62) Glu-lle-Gln-Leu-Nie-His-Asn-Leu-GIy-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg-Lys-Leu Leu-Gln-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to a synthesizer peptide automatic Protein Technologies PS3. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (O-allyl) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Frt? Oc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu -OH As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of the side chain to side chain After the described treatment procedures, the peptide bound to resin, containing amide, is returned to the instrument to complete the synthesis, the following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) ) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH and Fmoc-Glu (OtBu) -OH. A portion of about 50 mg of the peptide bound to resin is removed from the instrument, and the N-terminal Fmoc protecting group is removed for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 10 ml of DMF, 10 ml of THF and 10 ml of diethyl ether. The air-dried resin is suspended in 2 ml of TFA containing water, thioanisole, phenol and ethanedithiol in the proportions described above. After two hours, the TFA solution is filtered in 8 ml of tert-butylmethyl ether at 0 ° C, which precipitates the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 10 ml of 0.1% TFA and lyophilized to dryness. IS-MS: 3377 (M +).

EXAMPLE 69 Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg-Lys- Leu-Leu-GIn-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (AIIoc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu OH. As previously described, the resin-bound peptide is then removed from the instrument for deprotection of the side chain mediated by Pd, of the Lys (Alloc) and Asp (OaliIo) residues, and subsequent intramolecular cyclization of side chain to side chain.

After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His ( Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-IIe-OH, Fmoc-Glu (OtBu) -OH and Fmoc-Ser (tBu) -OH. A portion of about 50 mg of the resin-bound peptide is removed from the instrument, and the N-terminal Fmoc protecting group is removed for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 10 ml of DMF, 10 ml of THF and 10 ml of diethyl ether. The air-dried resin is suspended in 2 ml of TFA containing water, thioanisoi, phenol and ethanedithiol in the proportions described above. After two hours the TFA solution is filtered in 8 ml of terbutylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 10 ml of 0.1% TFA and lyophilized to dryness. JS-MS: 3463 (M +).

EXAMPLE 70 cycle (K18-D22) rNle8.K18.D22, L271hPTH (2-31) NH_. (SEQ ID NO: 64) Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-GIy-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg- Lys-Leu-Leu-Gln-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu OH. As previously described, the resin-bound peptide is then removed from the instrument for deprotection of the Pd-mediated side chain, from the Lys (Alloc) and Asp (Oaliio) residues, and subsequent intramolecular cyclization from side chain to side chain. After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are sequentially added: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His ( Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-GIn (Trt) -OH, Fmoc-lle-OH, Fmoc-GIu (OtBu) -OH, Fmoc-Ser (tBu) -OH and Fmoc-Val-OH. A portion of about 50 mg of the resin-bound peptide is removed from the instrument, and the N-terminal Fmoc protecting group is removed for 5 minutes, using 1 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 10 ml of DMF, 10 ml of THF and 10 ml of diethyl ether. The air-dried resin is suspended in 2 ml of TFA containing water, thioanisole, phenol and ethanedithiol in the proportions described above. After two hours the TFA solution is filtered in 8 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 10 ml of diethyl ether and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 10 ml of 0.1% TFA, and lyophilized to dryness. IS-MS: 3564 (M +).

EXAMPLE 71 cycle (K18-D22) rNle8.K18.D22, L271hPTH (7-34) NH? (SEQ ID NO: 65) Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg-Lys-Leu-Leu-Gin-Asp- Val-His-Asn-Phe amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide is placed with resin MBHA in a reaction vessel that is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Phe-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (AIIoc) -OH, Fmoc Ser (tBu) -OH, Fmoc-Asn (Trt) -OH and Fmoc-Leu-OH. As previously described, the resin-bound peptide is then removed from the instrument for deprotection of the Pd-mediated side chain, from the Lys (Alloc) and Asp (Oaliio) residues, and subsequent intramolecular cyclization from side chain to side chain. After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are added sequentially: Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-GIy-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His ( Trt) -OH; Fmoc-Nle-OH, Fmoc-Leu-OH. The crude peptide is divided from the resin and deprotected using 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol, and precipitated by adding the division mixture to cold terbutylmethyl ether. . The crude peptide is then purified by reverse phase liquid chromatography.

EXAMPLE 72 cycle (K10-D14) rA .NIe8-18.K10.P14.L271hPTH (1-31) NH9 (SEQ IP NO: 66) Ala-Val-Ser-Glu-lle-Gln-Leu-Nle-His- (Lys-Leu-G! Y-Lys-Asp) -Leu-Asn-Ser-NIe-Giu-Arg-Val-GIu-Trp- Leu-Arg-Lys-Leu-Leu-GIN-Asp-Val amide The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Glu (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-GIu (OtBu) -OH, Fmoc-Vai-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH; Fmoc-Nle-OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-Asp (Oalil) -OH; Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Lys (Alloc) -OH, Fmoc-His (Trt) -OH; Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. Wash successively the peptide bound to resin with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. A portion of the crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 85 mg of the final purified peptide, as a white solid. IS-MS: 3626 (M +). Amino acid analysis: Asp / Asn: 3.00 (3), Ser: 1.69 (2), GIu / Gln: 4. 91 (5), Gly: 0.94 (1), Wing: 0.91 (1), Val: 2.86 (3), He: 0.94 (1), Leu, 6.33 (6); Nie, 1.94 (2); Lys, 2.90 (3); His: 0.99 (1); Arg: 1 .96 (2); Trp: not determined (D- EXAMPLE 73 cycle (K14-D18) rA1, Nle8.K14, D18, L271hPTH (1-31) NH? (SEQ ID NO: 67) Ala-Val-Ser-Glu-lle-Gln-Leu-Nle-His-Asn-Leu-Gly-Lys- (Lys-Leu-Asn-Se-Asp) -Glu-Arg-Val-Glu-Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Vai-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu OH, Fmoc-Lys (Alloc) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. Wash successively the peptide bound to resin with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. A portion of the crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 75 mg of the final purified peptide, as a white solid. IS-MS: 3627 (M +). Amino acid analysis: Asp / Asn: 4.99 (4), Ser: 1.69 (2); Glu / Gln: 4. 86 (5), Gly: 0.94 (1), Ala: 0.98 (1); Val: 2.82 (3), lie: 0.90 (1); Leu: 6.35 (6); Nie: 0.87 (1), Lys: 2.89 (3); His: 1.00 (1); Arg: 1.91 (2); Trp: not determined (1 )- EXAMPLE 74 .8.18? X17 r »21 i 27-cycle (K ^ -D1) rA1.NIeB 1B.K1 /, D¿ \ L HhPTH (1-31) NH? (SEQ ID NO: 68) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn- (Lys-Nle-Glu-Arg-Asp) -Gu-Trp-Leu Arg-Lys-Leu-Leu-Gln-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide is placed with resin MBHA in a reaction vessel that is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-GIu (OtBu) -OH, Fmoc-Asp (Oalii ) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Nle-OH, Fmoc-Lys (Alloc) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu OH, Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. Wash successively the peptide bound to resin with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. Air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. A portion of the crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 136 mg of the final purified peptide, as a white solid. IS-MS: 3689 (M +). Amino acid analysis: Asp / Asn, 4.00 (4); Ser, 0.83 (1);, Glu / Gln, 4.84 (5); Gly, 0.93 (1); Ala, 0.96 (1), Val, 1.93 (2); He, 0.83 (1), Law, 6.32 (6), Nie, 1 .80 (2); Lys, 2.87 (3), His, 1.95 (2), Arg, 2.04 (2); Trp, not determined (1).

EXAMPLE 75 cycle (K21-D25) rA1.NIe8'18.K21, D25, L271hPTH (1-31) NH? (SEQ ID NO: 69) Ala-Val-Ser-Glu-lie-GIn-Leu-Nle-His-Asn-Leu-Gly-Lys-Hís-Leu-Asn-Ser-Nle-Glu-Arg- (Lys-Glu-Trp-Leu-Asp ) -Lys-Leu-Leu-Gln-Asp-Val amide. The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide is placed with resin MBHA in a reaction vessel that is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) ) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Nle-OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu OH, Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His- (Trt) -OH , Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val- OH and Fmoc-Ala-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. Wash successively the peptide bound to resin with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. A portion of the crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 131 mg of the final purified peptide, as a white solid. IS-MS: 3620 (M +). Amino acid analysis: Asp / Asn: 4.00 (4), Ser: 1.71 (2), Glu / GIn: 4. 84 (5), Gly: 0.96 (1), Wing: 0.97 (1), Val: 2.07 (2), He: 0.92 (1), Leu: 6.22 (6), Nie: 1.90 (2), Lys: 2.90 (3), His: 1.97 (2), Arg: 0.97 (1), Trp: not determined (1) - EXAMPLE 76 cycle (K25-D29) rA1, Nle8 18.K25, D29, L271hPTH (1-31) NH? (SEQ ID NO: 70) Ala-Val-Ser-Glu-lle-Gln-Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser-Nle-Glu-Arg-Val-Glu-Trp-Leu (Lys -Lys-Leu-Leu-Asp) -Asp-Vai amide. The peptide is prepared in a manner analogous to that previously described (method C). 0.5 mmol of Rink amide is placed with resin MBHA in a reaction vessel that is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Val-OH, Fmoc-Asp (OtBu) -OH, Fmoc-Asp (Oalil) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Boc) -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Val-OH , Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Nle-OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc -His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nie -OH, Fmoc-Leu-OH, Fmoc-GIn (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc Ala-OH. As previously described, the resin-bound peptide is then removed from the instrument for deprotection of the Pd-mediated side chain, the Lys (Alloc) and Asp (Oayilo) residues, and subsequent intramolecular cyclization from side chain to side chain. The Fmoc N-terminai protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. The peptide is washed successively bound to resin with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether.

The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. A portion of the crude peptide is then purified by reverse phase liquid chromatography, as previously described, to give 134 mg of the final purified peptide, as a white solid. IS-MS: 3591 (M +). Amino acid analysis: Asp / Asn: 4.11 (4), Ser: 1.69 (2); Glu / Gln: 3. 89 (4), Gly: 0.97 (1), Wing: 1 .00 (1), Val: 3.12 (3), lie: 0.92 (1); Leu: 6.45 (6), Nie, 1.85 (2), Lys: 3.02 (3), His: 1.92 (2), Arg: 0.98 (1), Trp: not determined (D- EXAMPLE 77 cycle (K, 118B-rD, 22?) R.?K/18B, rD »221hPTHrP (1 -34) NH2 (SEQ ID NO: 71) Ala-Val-Ser-Glu-His-GIn-Leu-Leu-His-Asp-Lys-Glu-Lys-Ser-He-Gln-Asp- (Lys-Arg-Arg-Arg-Asp) -Phe-Leu His-His-Leu-lle-Ala-Glu-lle-His-Thr-Ala amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Ala-OH, Fmoc-Thr (tBu) -OH, Fmoc-His (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ala-OH, Fmoc-lle-OH, Fmoc-Leu OH, Fmoc-His (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Leu-OH, Fmoc-Phe-OH, Fmoc-Asp (0-allyl) -OH, Fmoc-Arg (Pmc) - OH, Fmoc-Arg (Pmc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Lys (AIIoc) -OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, Fmoc-ile -OH As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are added sequentially: Fmoc-Ser (tBu) -OH, Fmoc-Lys (Boc) -? H, Fmoc Gly-OH, Fmoc-Lys (Boc-OH, Fmoc-Asp (OtBu) -OH, Fmoc-His (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH , Fmoc-His (Trt) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. The resin-bound peptide is then removed from the instrument and the N-terminal Fmoc protecting group is removed for 5 minutes, using 17 ml of a 20% piperidine / DMF solution, the resin-bound peptide is washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of Diethyl ether The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol.After two hours the TFA solution is filtered through the 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide, centrifuge the peptide mixture at 2500 rpm for 5 minutes and decant, re-suspend the crude white solid in 120 ml of ether diethyl, centrifuged and decanted. This procedure is repeated four times washing and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and lyophilized to dryness. The crude peptide is then purified by reverse phase liquid chromatography to give 10 mg of the final peptide as a white solid. IS-MS: 3980 (M +). Amino acid analysis: Asp / Asn: 3.11 (3), Thr: 1.05 (1), Ser: 1.78 (2), Giu / Gln: 3.93 (4), Gly: 0.8 (1), Wing: 3.12 (3), Val: 1.00 (1), He: 2.73 (3), Leu: 4.00 (4), Lys: 2.86 (3), Phe: 1.13 (1), His: 4.93 (5), Arg: 3.12 (3).

EXAMPLE 78 cycle (K18-D22) rK18 26 '? 0, D22.L23'28 31, E25'291hPTHrP (1-34) NH? (SEQ ID NO: 72) Ala-Val-Ser-GIu-His-GIn-Leu-Leu-His-Asp-Lys-Gly-Lys-Ser-lle-Gln-Asp- (Lys-Arg-Arg-Arg-Asp) -Leu-Leu Glu-Lys-Leu-Leu-Glu-Lys-Leu-His-Thr-Ala-amide. The peptide is prepared in a manner analogous to that previously described (method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPPS based on Fmoc: Fmoc-Ala-OH, Fmoc-Thr (tBu) -OH, Fmoc-His (Trt) -OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Lys (Boc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Leu-OH , Fmoc-Leu-OH, Fmoc-Asp (Oalil) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Lys (Alloc) - OH, Fmoc-Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH and Fmoc-lle-OH. As previously described, the resin-bound peptide is then taken out of the instrument for deprotection of the Pd-mediated side chain, of the Lys (Alloc) and Asp (Oalyl) residues, and subsequent intramolecular cyclization of side chain to side chain. After the described treatment procedures, the peptide bound to resin, which contains amide, is returned to the instrument to complete the synthesis; The following amino acids are added sequentially: Fmoc-Ser (tBu) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Lys (Boc) -OH, Fmoc-Asp (OtBu) -OH, Fmoc-His (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-GIu (OtBu) -OH, Fmoc Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. The resin-bound peptide is then removed from the instrument and the N-terminal Fmoc protecting group is removed for 5 minutes, using 20 ml of a 20% piperidine / DMF solution. The crude peptide is divided from the resin and deprotected using 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol, and precipitated by adding the partition mixture to ether terbutylmethyl. The crude peptide is then purified by reverse phase liquid chromatography, to give 31 mg of final peptide, as a white solid. IS-MS: 3986 (M +). Amino acid analysis: Asp / Asn: 2.60 (3), Thr: 1.26 (1), Ser: 1.61 (2), Glu / Gln: 5.02 (5), Gly: 0.96 (1), Ala: 2.37 (2); Val: 0.96 (1), He: 0.81 (1); Leu: 7.71 (7), Lys, 5.17 (5), His: 3.17 (3), Arg: 2.37 (3).

EXAMPLE 79 bicyclo (K13-D17, K18-D22) rA1, Nle8, D 7'22.K18, L27lhPTH (1-31) NH? (SEQ ID NO: 73) Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-Gly- (Lys-Hys-Leu- Asn-Asp) - (Lys-Glu-Arg-Val-Asp) - Trp-Leu-Arg-Lys-Leu-Gln-Asp-Val amide.

A portion of approximately 0.5 mmol of the previously bound resin-bound peptide terminating with the amide bridge D22-K18 is returned to the automatic peptide synthesizer and the N-terminal Fmoc protecting group is removed, as described above. The following amino acid residues are successively added using standard methods of HBTU coupling: Fmoc-Asp (Oalil) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, and Fmoc-Lys (Alloc) -OH. The resin is removed from the instrument and washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether, then air-dried. The allyl and Alloc protecting groups are removed under Pd catalysis, as previously described, and the cyclization is carried out between the Asp17 and K13 residues in two cycles, using 284 mg of HBTU, 101 mg of HOBt and 165 ml of NMM in 20 ml of DMF. The resin is successively washed with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The resin is returned to the instrument and the synthesis is completed after the addition of the following amino acids: Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-ile-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. The N-terminal Fmoc protecting group is removed for 5 minutes using 17 ml of a 20% piperidine / DMF solution. The resin-bound peptide is removed from the instrument and washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol.

After two hours the TFA solution is filtered in 160 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted.

The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This procedure is repeated sidewise four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. The crude peptide is purified by reverse phase high performance liquid chromatography, as previously described, to give 13 mg of final peptide, as a white solid. IS-MS: 3643 (M +). Amino acid analysis: Asp / Asn: 4.83 (5), Ser: 0.97 (1), Glu / Gln: 3. 98 (4), Gly: 0.97 (1), Wing: 0.96 (1), Val: 3.14 (3), lie: 0.88 (1), Leu: 6.47 (6), Nie: 0.80 (1), Lys: 2.91 (3), His: 2.03 (2), Arg, 2.07 (2); Trp: not determined (1). The position of the amide bridges is confirmed by Edman degradation.

EXAMPLE 80 Ala-Val-Ser-Glu-lle-GIn-Leu-Nle-His-Asn-Leu-GIy-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu Arg- (Lys-Leu-Leu-Gln-Asp) -Val amide.

The title compound is prepared in a manner analogous to that previously described. Load 0.80 g (0.45 mmol) Rink amide with resin MBHA (Nova Biochem, La Jolla, CA, E.U.A.) in the reaction vessel and swelled for 10 minutes using 10 ml of DMF. The following amino acid residues are added successively, using standard methods of coupling with HBTU: Fmoc-Val-OH, Fmoc-Asp (Oalil) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc-Lys (Alloc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, and Fmoc-Trp (Boc) -OH. The resin is removed from the instrument and washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether, then air-dried. The Alilo and Alloc protective groups are removed under Pd catalysis, as previously described and the cyclization is obtained between the Asp30 and K36 residues in two cycles using 284 mg of HBTU, 101 mg of HOBt and 165 ml of NMM in 20 ml. of DMF. The resin is then washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The resin is returned to the instrument and the synthesis is completed after adding the following amino acids: Fmoc-Asp (Oalil) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH , Fmoc-Lys (Alloc) - OH, Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) - OH, Fmoc-Lys (Boc) - OH, Fmoc-Gly-OH; Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-GIn (Trt) -OH, Fmoc-lle-OH , Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH; Fmoc-Val-OH and Fmoc-Ala-OH. The resin is removed from the instrument, washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and air dried. It eliminates Alilo and Alloc protective groups under Pd catalysis, as previously described, and the cyclization between the Asp22 and K18 residues is achieved in two cycles using 284 mg of HBTU, 101 mg of HOBt and 165 ml of NMM in 20 ml of DMF. The resin is subsequently washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The protective group is removed N-terminal Fmoc for 5 minutes using 25 ml of a 20% piperidine / DMF solution. The resin-bound peptide is successively washed with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After two hours the TFA solution is filtered in 120 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. The crude peptide is purified by reverse phase high performance liquid chromatography, as previously described to provide 90 mg of the final peptide, as a white solid. 1S-MS: 3615 (M +). Amino acid analysis: Asp / Asn: 3.79 (4), Ser: 1.84 (2), Glu / Gln: 3.84 (4), Gly: 1.19 (1), Wing: 1.00 (1), Val: 2.82 (3), He: 0.89 (1), Leu: 6.16 (6), Nie: 0.74 (1), Lys (2.73 (3); His: 1.94 (2), Arg: 1.92 (2), Trp: not determined (1 ). The position of the amide bridges is confirmed by Edman degradation.

EXAMPLE 81 bicycles (K13-D17.K18-P22) rA1.NIe8.P17 22.K18.L271hPTH (1-34) NH (SEQ IP NO: 75) Ala-Val-Ser-Glu-lle-Gln-Leu-Nle-His-Asn-Leu-Gly- (Lys-His-Leu-Asn-Asp) - (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg-Lys-Leu-Leu-Gln-Asp-Val-His-Asn-Phe amide. A portion of approximately 0.46 g (approximately 1.0 mmol) of the resin-bound peptide, prepared previously, which starts with Phe34 and ends with the amide bridge Asp22-Lys18 is returned to the automatic peptide synthesizer and the protective group Fmoc N- is removed. terminal, as described above. The following amino acid residues are successively added, using standard methods of coupling with HBTU: Fmoc-Asp (Oalil) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, and Fmoc-Lys (Alloc) -OH. The resin is then removed from the instrument, washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and air dried. The allyl and alloc protecting groups are eliminated as previously described and the cyclization between residues Lys13 and Asp17 is obtained, in two cycles, using HBTU, HOBt and NMM. After washing and drying, the resin is returned to the instrument and the synthesis is completed by adding the following amino acids in the indicated order: Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) - OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH , Fmoc-Val-OH and Fmoc-Ala-OH. The crude peptide is divided from the resin and deprotected using 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol, and precipitated by the addition of the division mixture, to cold tert-butyl ether. The crude peptide is then purified by reverse phase liquid chromatography.

EXAMPLE 82 Bicycles (K13-D17.K2ß-P30) rA1.NIe8 18.P17, L271hPTH (1-31) NH? (SEQ IP NO: 76) Ala-Val-Ser-Glu-lle-Gln-Leu-Nle-His-Asn-Leu-Gly- (Lys-His-Leu-Asn-Asp) -Nle-GIu-Arg-Val-Glu-Trp-Leu Arg- (Lys-Leu-Leu-Gln-Asp) -VaI amide. The title compound is prepared in a manner analogous to that previously described. 0.80 g (0.45 mmol) of Rink amide is charged with MBHA resin (Nova Biochem, La Jolla, CA, E. U. A.), in a reaction vessel and swelled for 10 minutes using 10 ml of DMF. The following amino acid residues are successively added, using standard methods of coupling with HBTU: Fmoc-Val-OH, Fmoc-Asp (Oalil) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu -OH, Fmoc- Lys (Alloc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH and Fmoc-Trp (Boc) -OH. The resin is removed from the instrument and washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether, then air-dried. The allyl and Alloc protecting groups are removed under Pd catalysis, as previously described and the cyclization is carried out between the Asp30 and K26 residues in two cycles, using 284 mg of HBTU, 101 mg of HOBt and 165 ml of NMM in 20 ml of DMF. The resin is then washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The resin is returned to the instrument and the synthesis is completed after the addition of the following amino acids: Fmoc-GIu (OtBu) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Nle-OH, Fmoc-Asp (Oalil) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, Fmoc-Lys (Alloc) -OH , Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) - OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. The resin is then removed from the instrument, washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and air dried. The allyl and Alloc protective groups are again removed under Pd catalysis, as previously described, and the cyclization is again obtained between the Asp22 and K18 residues in two cycles, using 284 mg of HBTU, 101 mg of HOBt and 165 ml of NMM in 20 ml of DMF. The resin is then washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The N-terminal Fmoc protecting group is removed for 5 minutes using 25 ml of a 20% piperidine / DMF solution.

The resin-bound peptide is successively washed with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1. 0 ml of ethanedithiol. After 2 hours the TFA solution is filtered in 120 ml of tert-butylmethyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in 100 ml of water containing 0.1% TFA and lyophilized to dryness. The crude peptide is purified by reverse phase high performance liquid chromatography, as previously described, to give 22 mg of final peptide, as a white solid. IS-MS: 3642 (M +). Amino acid analysis: Asp / Asn: 4.00 (4), Ser: 0.99 (1), Glu / Gln: 4. 95 (5), Gly: 0.96 (1), Wing: 0.95 (1), Val, 3.05 (3), He, 0.92 (1), Leu, 6.40 (6), Nie, 1.78 (2), Lys: 1.81 (2), His, 2.17 (2), Arg: 2.03 (2), Trp: not determined (1). The position of the amide bridges is confirmed by Edman degradation.

EXAMPLE 83 Leu-Leu-His-Asp-Lys-Gly-Lys-Ser-lle-Gln-Asp- (Lys-Arg-Arg-Arg-Asp) -Phe-Leu-His-His-Leu-lle-Ala-Glu- lle-His-Thr-Ala amide. The peptide is prepared in a manner analogous to that previously described (Method B). 0.5 mmol of Rink amide with MBHA resin is placed in a reaction vessel which is then attached to an automatic Protein Technologies PS3 peptide synthesizer. The following amino acids are sequentially added in a manner consistent with SPMS BASED ON Fmoc: Fmoc-Ala-OH, Fmoc-Thr (tBu) -OH, Fmoc-His (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ala-OH, Fmoc-lle-OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Leu-OH, Fmoc Phe-OH, Fmoc-Asp (Oalil) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Lys (Alloc) -OH, Fmoc -Asp (OtBu) -OH, Fmoc-Gln (Trt) -OH, and Fmoc-lle-OH. As previously described, the resin-bound peptide is removed from the instrument for Pd-mediated side chain deprotection of Lys (AIIoc) and Asp (Oalyl) residues and subsequent intramolecular cyclization of side chain to side chain. After the described treatment procedures, the peptide bound to the amide-containing resin is returned to the instrument to complete the synthesis: the following amino acids are sequentially added: Fmoc-Ser (tBu) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Lys (Boc) -OH, Fmoc-Asp (OtBu) -OH, Fmoc-His (Trt) -OH, Fmoc-Leu OH and Fmoc-Leu-OH. The crude peptide is divided from the resin and deprotected using 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol and precipitated by addition of the division mixture to tert-butyl methyl ether. cold. The crude peptide is then purified by rse phase liquid chromatography.

EXAMPLE 84 Leu-Nle-His-Asn-Leu-Gly- (Lys-His-Leu-Asn-Asp) - (Lys-GIu-Arg-Val-Asp) -Trp-Leu-Arg-Lys-Leu-Leu-Gln- Asp-Val-His-Asn-Phe amide. A portion of the resin-bound peptide terminating with the amide bridge Lys18-Asp22, in Example 23, is returned to the automatic peptide synthesizer and the N-terminal Fmoc protecting group is removed, as described above. The following amino acid residues are successively added, using common procedures and coupling currents with HBTU: Fmoc-Asp (Oail) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) - OH and Fmoc-Lys (Alloc) -OH. The resin is then removed from the instrument, washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and air dried. The allyl and alloc protecting groups are removed as previously described and the cyclization is carried out between the Lys13 and Asp17 residues in two cycles, using HBTU, HOBt and NMM. After washing and drying the resin is returned to the instrument and the synthesis is completed, adding the following amino acids in the indicated order: Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH. The crude peptide is divided from the resin and deprotected using 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol, and precipitated by addition of the partition mixture to the ether. cold tertiary butyl. The crude peptide is then purified by rse phase liquid chromatography.

EXAMPLE 85 bicyclo (K18-D2Z, K? -D3U) rNle 8B,? Kx118B, rD.2; ¿2,, L 27? HPTH (7-34) NH2 (SEQ ID NO: 79) Leu-Nle-His-Asn-Leu-Gly-Lys-His-Leu-Asn-Ser- (Lys-Glu-Arg-Val-Asp) -Trp-Leu-Arg- (Lys-Leu-Leu-Gln-Asp ) -Val-His-Asn-Phe amide. The title peptide is prepared in a manner analogous to that previously described. 0.75 g (0.41 mmol) of Rink amide is charged with MBHA resin (Nova Biochem, La Jolla, CA, E. U. A.), in a reaction vessel and swelled for 10 minutes using 10 ml of DMF. The following amino acid residues are successively added, using standard methods of HBTU coupling: Fmoc-Phe-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Val-OH, Fmoc-Asp (Oalil) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc-Leu-OH and Fmoc-Lys (Alloc) -OH. The resin is then removed from the instrument, washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and air dried. The allyl and protective groups are removed alloc, as previously described and the cyclization between residues Lys26 and Asp30 is obtained in two cycles using HBTU, HOBt and NMM. After washing and drying the resin is returned to the instrument and the following amino acid residues are added using the coupling conditions described: Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH, Fmoc-Trp (Boc) -OH, Fmoc-Asp (Oalyl) -OH, Fmoc-Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, and Fmoc-Lys (Alloc) -OH. The resin is then removed from the instrument, washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and dried on air. The protective groups aliio and alloc are eliminated, as previously described and the cyclization between residues Lys18 and Asp22 is achi in two cycles, using HBTU, HOBt and NMM. After washing and drying the resin is returned to the instrument and the synthesis is completed by adding the following amino acid residues in the indicated order: Fmoc-Ser (tBu) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH , Fmoc-His (Trt) -OH, Fmoc-Lys (Boc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc -Nle-OH, Fmol-Leu-OH. The crude peptide is divided from the resin and deprotected using 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol, and precipitated by addition of the partition mixture to ether. terbutylmethyl. The crude peptide is then purified by rse phase liquid chromatography.

EXAMPLE 86 tricycle (K13-D17, K18-D22, K26-D30) rA \ Nle8, K18, D17 22.L271hPTH (1-31) NH9 (SEQ ID NO: 80) Ala-Val-Ser-Glu-lle-Gln-Leu-Nle-His-Asn-Leu-GIy- (Lys-His-Leu-Asn-Asp) - (Lys-Glu-Arg-Val-Asp) -Trp- Leu-Arg- (Lys-Leu-Leu-Gln-Asp) -Val amide. The title compound is prepared in a manner analogous to that previously described. 0.80 g (0.45 mmol) of Rink amide is charged with MBHA resin (Nova Biochem, La Jolla, CA, E. U. A.), in a reaction vessel and swelled for 10 minutes using 10 ml of DMF. The following amino acid residues are added, successively, using standard methods of coupling with HBTU: Fmoc-Val-OH, Fmoc-Asp (Oalil) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Leu-OH, Fmoc Leu-OH, Fmoc-Lys (Alloc) -OH, Fmoc-Arg (Pmc) -OH, Fmoc-Leu-OH and Fmoc-Trp (Boc) -OH. The resin is removed from the instrument and washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and then air-dried. The allyl and alloc protecting groups are removed under Pd catalysis, as previously described and the cyclization between the residues Asp20 and K26 is obtained in two cycles, using 284 mg of HBTU, 101 mg of HOBt and 165 μl of NMM in 20 ml of DMF. The resin is then washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The resin is returned to the instrument and the synthesis is continued, adding the following amino acids: Fmoc-Asp (Oalil) -OH, Fmoc Val-OH, Fmoc-Arg (Pmc) -OH, Fmoc-Glu (OtBu) -OH, Fmoc-Lys (Alloc) -OH. The resin is removed from the instrument and washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether, and then air-dried. The allyl and alloc protecting groups are eliminated by Pd catalysis and the cyclization between residues Asp18 and K22 is obtained in two cycles, using 284 mg of HBTU, 101 mg of HOBt and 165 ml of NMM in 20 ml of DMF. The resin is then washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The resin is returned to the instrument and the synthesis is completed by adding the following amino acids: Fmoc-Asp (Oalil) -OH, Fmoc-Asn (Trt) -OH, Fmoc-Leu-OH, Fmoc-His (Trt) -OH, Fmoc -Lys (Alloc) -OH, Fmoc-Gly-OH, Fmoc-Leu-OH, Fmoc-Asn (Trt) -OH, Fmoc-His (Trt) -OH, Fmoc-Nle-OH, Fmoc-Leu-OH, Fmoc-Gln (Trt) -OH, Fmoc-lle-OH, Fmoc-Glu (OtBu) -OH, Fmoc-Ser (tBu) -OH, Fmoc-Val-OH and Fmoc-Ala-OH. The resin is again removed from the instrument, washed successively with 100 ml of DMF, 100 ml of THF, 100 ml of diethyl ether and air dried. The allyl and alloc protecting groups are removed under Pd catalysis, as previously described, and the cyclization is obtained between the Asp17 and K13 residues in two cycles, using 284 mg of HBTU, 101 mg of HOBt and 165 ml of NMM in 20 ml of DMF. The resin is then washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The N-terminal Fmoc protecting group is removed for 5 minutes, using 25 ml of a 20% piperidine / DMF solution. The resin-bound peptide is washed successively with 100 ml of DMF, 100 ml of THF and 100 ml of diethyl ether. The air-dried resin is suspended in 40 ml of TFA containing 2.0 ml of water, 2.0 ml of thioanisole, 3.0 g of phenol and 1.0 ml of ethanedithiol. After 2 hours the TFA solution is filtered in 120 ml of terbutyl ether at 0 ° C, which effects the precipitation of the crude peptide. The peptide mixture is centrifuged at 2500 rpm for 5 minutes and decanted. The crude white solid is resuspended in 120 ml of diethyl ether, centrifuged and decanted. This washing procedure is repeated four times and the resulting peptide is vacuum dried, dissolved in water containing 100 ml of 0.1% TFA and freeze-dried to dryness. The crude peptide is purified by reverse phase high performance liquid chromatography, as previously described, to give 16 mg of final peptide, as a white solid. IS-MS: 3625 (M +). Amino acid analysis: Asp / Asn: 4.88 (5); Ser: 0.95 (1); Glu / GIn: 4. 00 (4), Glu: 1.01 (1), Wing: 0.97 (1), Vai: 2.93 (3); He: 0.93 (1), Leu: 641 (6), Nie: 0.84 (1), Lys: 2.73 (3), His: 2.28 (2), Arg: 2.07 (2); Trp: not determined (D- PHARMACEUTICAL COMPOSITIONS The peptide compounds of formula I exhibit useful pharmacological activity and, consequently, are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders.

More especially, some peptide compounds within the scope of the invention bind PTH receptors and stimulate adenylyl cyclase activity. The increased adenylyl cyclase activity is associated with the positive growth of the bones and, therefore, for example, the peptide compounds of the invention are useful for the treatment of physiological conditions including: hypocalcemia, osteoporosis, osteopenia and associated disorders with osteoporosis and osteopenia, such as hyperparathyroidism and Cushings syndrome; osteopenia induced by glucocorticoids and by immunosuppressants; and repair of fractures and bone refractures. Additionally, some peptide compounds of formula I bind to PTH receptors but do not stimulate adenylyl cyclase activity. These peptide compounds are useful in the treatment of disease states characterized by an excess of PTH, including hyperkalemia crises related to hyperparathyroidism and hyperparathyroidism, malignant hypercalcemia, renal failure and hypertension. A special embodiment of the therapeutic methods of the present invention is the treatment of osteoporosis. The reference herein to treatment should be understood to include prophylactic therapy, as well as treatment of established conditions. The present invention also provides pharmaceutical compositions comprising peptide compounds of the present invention, formulated together with one or more pharmaceutically acceptable, non-toxic carriers. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, intrapulmonally, transmucosally, intraocularly, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, typically (as by powders, ointments or drops), transdermal, iontophoretic, buccal , or as an oral or nasal spray.

Intrapulmonary delivery and subcutaneous delivery are especially preferred administration methods for the peptide compounds of the present invention. The term "parenteral" administration, as used herein, refers to modes of administration that include intravenous, intramuscular, intraperitoneal, intrastretch, subcutaneous, and intra-articular injection, as well as infusion. The pharmaceutical compositions of the invention, for parenteral injection, comprise sterile, pharmaceutically acceptable solutions, dispersions, suspensions or emulsions, aqueous or non-aqueous, as well as sterile powders for reconstitution to injectable, sterile solutions or dispersions, just before use. Examples of suitable carriers, diluents, solvents or vehicles, aqueous and non-aqueous, include: water, ethanoi, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), and suitable mixtures thereof; vegetable oils (such as olive oil) and injectable organic esters, such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by maintaining the required particle size, in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants, such as preservatives, wetting agents, emulsifying agents and dispersing agents. The prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example: paraben, chlorobutanol, phenol, sorbic acid and the like. It may also be convenient to include isotonic agents, such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be effected by the inclusion of agents that delay absorption, such as aluminum monostearate and gelatin. In some cases, in order to prolong the effect of the drug, it is convenient to stop the absorption of the drug from the subcutaneous or intramuscular injection. This can be achieved by the use of a liquid suspension of crystalline or amorphous material, with low water solubility. The suspension may contain additional excipients, such as trihalose. The absorption rate of the drug then depends on its rate of dissolution which, in turn, may depend on the size of the crystal and the crystalline form. Alternatively, the delayed absorption of a parenterally administered drug is achieved by dissolving or suspending the drug in an oily vehicle.

Injectable depot forms are formed by forming microencapsulation matrices of the drug in biodegradable polymers, such as polylactide-polyglycolide. Depending on the drug to polymer ratio and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly (orthoesters) and poly (anhydrides). Depot injectable formulations are also prepared by trapping the drug in liposomes or microemulsions, which are compatible with body tissues. Injectable formulations can be sterilized, for example, by filtration through a bacteria retainer filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium, just prior to use. Solid dosage forms for oral administration include: capsules, tablets, pills, powders and granules. In said solid dosage forms, the active peptide compound is mixed with at least one pharmaceutically acceptable inert excipient or carrier, such as sodium citrate or dicalcium phosphate and / or (a) fillers or extenders, such as starches, lactose, sucrose, glucose , mannitol and silicic acid; b) binders, such as, for example, carboxymethyl cellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and acacia gum; c) humectants, such as glycerol; d) disintegrating agents, such as agar-agar, calcium carbonate, potato starch or tapioca, aiginic acid, certain silicates and sodium carbonate; e) solution retarding agents, such as paraffin; f) absorption accelerators, such as quaternary ammonium compounds; g) wetting agents, such as, for example, cetyl alcohol and glycerol monostearate; h) absorbers, such as kaolin and bentonite clay; and i) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium laurisulfate and their mixtures. In the case of capsules, tablets and pills, the dosage form may also comprise pH regulating agents. Solid compositions of a similar type can also be employed as fillers in soft gelatin capsules and filled gelatin capsules, using excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols, and the like. The solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared with coatings and layers, such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of a composition that they release the active ingredient (s) only, or preferably, in a certain part of the intestinal tract; optionally in a delayed manner. Examples of the embedding compositions that can be used include polymeric substances and waxes.

The active peptide compounds may also be in. micro-encapsulated form, if appropriate, with one or more of the aforementioned excipients. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents, such as those commonly used in the art, such as, for example, water or other solvents; solubilizing and emulsifying agents, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular cottonseed, ground nut oils) , corn, germ, olive, castor bean, sesame), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and sorbitan fatty acid esters, and their mixtures. In addition to inert diluents, the oral compositions may also include adjuvants, such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents. The suspensions, in addition to the active compounds, may contain suspending agents, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, as well as mixtures thereof.

Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with non-irritating excipients or carriers, such as cocoa butter, polyethylene glycol or a suppository wax, which is solid at room temperature, but liquid at the temperature of the body and, therefore, melts in the rectum or in the vaginal cavity, and releases the active peptide compound. For delivery to the buccal or sublingual membranes, oral dosage forms are typically used as pills, tablets or capsules, as described hereinabove. Alternatively, the formulation can be applied to the oral mucosa with an adhesive, such as hydroxypropic cellulose, as described in U.S. Patent No. 4,940,587, incorporated herein by this reference. This formulation allows the controlled release of the drug in the mouth and through the buccal mucosa. The compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are derivatives in general of phospholipids or other lipid substances. Liposomes are formed by hydrated, monolaminar or multilamellar liquid crystals, which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The compositions herein in liposome form may contain, in addition to a peptide compound of the present invention, stabilizers, preservatives, excipients and the like. The lipids preferred are phospholipids and phosphatidylcholines (lecithins), both natural and synthetic. Methods for forming liposomes are known in the art.

See, for example, Precott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, NY (1976), pages 33 et seq. Dosage forms for topical administration of a peptide compound of this invention include: powders, sprays, ointments and inhalations. The active peptide compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any pharmaceutically acceptable preservatives, pH regulators or propellants, which may be necessary. Ophthalmic formulations, eye ointments, powders and eye solutions are also contemplated within the scope of this invention. The peptide compounds of this invention can be delivered transdermally by iontophoresis. In general iontophoresis refers to the transport of ionic solutes through biological membranes, under the influence of an electric field. The iontophoretic delivery of the drug has the ability to bypass gastrointestinal and hepatic "first-pass" effects, which make the enteric routes to administer peptides relatively ineffective. In general, the iontophoretic devices comprise at least two electrodes, a source of electrical energy and at least one reservoir containing the peptide compound to be delivered. He The reservoir can be in the form of any suitable material for making contact between the iontophoresis unit and the skin. Suitable materials include: foams, gels and matrices. The iontophoresis gels can be karaya gum, other polysaccharide gels or similar hydrophilic aqueous gels, capable of carrying ions. Representative gels include: polyvinyl alcohol, polymethylpyrrolidine, methylcellulose, polyacryiamide, polyhemas, polyheme derivatives and the like. The selected matrix must have no irritant properties to avoid irritation to the skin or tissue of the patient; suitable conductivity properties to obtain good electrical contact with the skin or tissue, and the ability to act as a carrier medium for the peptide compound. Other means for the iontophoretic delivery of the peptide compounds include a patch comprising the peptide compound as well as reusable or rechargeable iontophoretic devices. The iontophoretic delivery of the peptides is described in US Patent 5, 494,679. The iontophoretic delivery of hPTH analogs is discussed in W0 95/11988-A1. Another method of transdermal delivery is the needleless system developed by PowderJect Pharmaceuticals (Magdalen Center, Oxford Science Park, Oxford 0X4 4GA, United Kingdom), in which a jet of helium gas is used to deliver drugs through the skin or through the skin. the mucosa of the mouth. In particular, it accelerates the drug's powder to around 750 m / second for about 3 milliseconds, thereby allowing the powders to pass into or around the cells of the skin and into the systemic circulation of the patient. Preferably, the intrapulmonary or intranasal delivery of the peptide compound is achieved by administering an aerosol to the patient's bronchioles or nasal passages, using a dosing inhalation device (MDL, acronym for its English designation: Metered Dose Inhalation). For use in the MDl, the peptide compound is dissolved or suspended in a physiologically inert aerosol propellant. The propellants useful in MDl devices include chlorofluorocarbons (CFCs), such as CFC-11 (trifluorochloromethane), CFC-12 (dichlorodifluoromethane) and CFC-114 (dichlorotetrafluoroethane) and non-chlorofluorocarbons (NCFC) which include alkanes such as HCFC-123 (1, 1, 1-trifluoro-2,2-dichloroethane), HCFC-124 (1,1,1,2-etrafiuorochloroethane), HCFC-141 b, HCFC-225, HFC-125, FC-C51-12 ( perfluorodimethyl-cyclobutane), DYMEL A (dimethyl ether) DYMEL 152a (1, 1- difluoroethane). The peptide compound can be dissolved in the propellant or it can take the form of a droplet suspension or a fine dispersion of solid particles. The aerosol composition may also contain additional cosolvents, surfactants, excipients and flavoring or taste masking agents. Surfactants are necessary to prevent aggregation (in the form of "cake" or crystallization, for example) of the medicinally active peptide compound in the reservoir of the inhaler, to facilitate uniform dosing when administering the aerosol, and to give an aerosol spray discharge having a favorable respirable fraction (ie, a particle size distribution such that a large portion of the discharge reaches the alveoli where absorption takes place and, thereby, produces high deposition efficiencies in the lung). Surfactants useful in the formulation of aerosols in CFC propellants are well known in the art. Representative surfactants include: oleic acid, sorbitan trioleate and various long chain diglycerides and phospholipids. Halogenated alkane propellants, such as HFC-134a and HFC-227ea are substantially less polar than traditional CFC propellants and it has been found that many surfactants that are generally used in known MDl formulations are immiscible with, or insoluble in, these new non-CFC propellants, and therefore, They are incompatible with them. US Patent 5,225,183 discloses a formulation comprising HFC-134a, a surfactant and an adjuvant or cosolvent having greater polarity than HFC-134a. Representative adjuvants or cosolvents having greater polarity than HFC-134a include alcohols, such as ethanol, isopropanol and propylene glycol; hydrocarbons such as propane, butane, isobutane, pentane, isopentane and neopentane; and other propellants such as propellers 11, 12, 1 14, 113 and 142b. People say that The adjuvant provides a propellant system that has properties comparable to those of CFC-based propellants and, therefore, allows the use of traditional surfactants. Mixtures of HFC-134a with other solvents or propellants, including dimethyl ether, fluorocarbons, such as perfluoropropane, perfluorobutane and perfluoropentane, and hydrochlorofluorocarbons, such as HCFC-123, are described in U.S. Patent No. 5,190,029. Another way to solve the incompatibility of HFC-134a with many surfactants is to replace with other surfactants those traditionally used in CFC aerosols. The use of polar surfactants, such as polyethylene glycol, diethylene glycol monoethyl ether, polyoxyethylene (20) sorbitan monooleate, propoxylated polyethylene glycol and polyoxyethylene (4) lauryl ether, is described in U.S. Patent 5,492,688, incorporated herein by this reference. U.S. Patent No. 5,182,097, which is incorporated herein by this reference, discloses that HFC-134a can be used as the sole propellant if oleic acid is used as the surfactant. U.S. Patent No. 5,182,097, incorporated herein by reference, discloses that the use of fluorinated surfactants allows the use of HFC-134a as the sole propellant. The application of TCP No. W091 / 11 173 discloses that mixtures of fluorinated surfactants with conventional surfactants or other adjuvants, such as poioxamers or polyethylene glycols, allow the use of hydrofluorocarbon propellants. The non-conventional excipients that have been used to prepare aerosol formulations with halogenated alkane propellants, include protective colloids; see TCP request No. W095 / 15151 and tocopherol, see TCP request No. W095 / 24892. Suspension aerosol formulations are prepared by combining any surfactants, excipients and flavoring or taste-masking agents, with a peptide compound that has been ground or otherwise reduced to the desired particle size, and placing the mixture in a container or ampoule for proper spray. After sealing the container, aerosol propellant is introduced and the system is stirred to completely combine the ingredients. In some cases it may be necessary to wet grind the peptide compound in a closed system, such as, for example, under temperature and pressure conditions that allow the peptide compound to be ground while mixing with a liquid phase aerosol propellant. It is expected that, for any particular combination of peptide compound, propellant and excipients, the ideal order of addition of the ingredients and the conditions under which they are to be combined can be easily determined. In addition to supplying by means of metered dose inhalers, other pulmonary delivery systems include dry powders and liquid solutions or suspensions suitable for nebulization. Aqueous or non-aqueous solutions or dispersions can also be administered by tracheal instillation.

Dry powder formulations will typically comprise the peptide compound in a dry form, usually lyophilized, with a particle size within the preferred range for deposition within the alveolar region of the lung. The particle size preferably is about 0.5 μm to 5 μm. Particles within the preferred size scale can be produced by a variety of techniques well known in the art, including jet milling, spray drying, solvent precipitation and the like. Dry powders are administered to the patient in conventional dry powder inhalers (DPIs), which use the inspiratory breathing pass, in patients, or an air-assisted device, which uses a source external to the powder to disperse the powder in a spray cloud. The peptide compound can be combined with a dry, pharmaceutically acceptable, volume-forming powder. Preferred, dry bulk-forming powders include: sucrose, lactose, trehalose, human serum albumin (HSA, acronym for its English designation: Human Serum Albumin) and glycine. Other suitable dry body-building powders include: celubiosa, dextrans, maltotriose, pectin, sodium citrate, sodium ascorbate, mannitol and the like. Liquid formulations of peptide compound for nebulization may employ slightly acidic regulators (pH 4-6) including acetate, ascorbate and citrate. These regulators can act as antioxidants, or other antioxidants can be added pharmaceutically acceptable to protect any udder methionine against oxidation. Other agents can be added to increase or maintain chemical stability, including chelating agents, protease inhibitors, isotonic modifiers, inert gases and the like. Aqueous solutions or suspensions of the peptide compound can be administered by intratraqueai instillation. The aqueous vehicle is selected from pure water, substantially pure water or water combined with other excipients, such as salts, excipients or other excipients such as those described above, which are generally used in water-based systems. The liquid formulations are in the form of dispersions or solutions based on solution, in solvents or cosolvents, such as alcohols or glycols, with water. Non-aqueous solutions include systems based on alcohol or glycol, which may have some water, but which are not constituted by a majority percentage of water, and which are known to those skilled in the art as effective and safe delivery vehicles. The actual dose levels of active ingredient in the pharmaceutical compositions of this invention may be varied in order to obtain an amount of active peptide (s) (s) which is effective to obtain the desired therapeutic response for a particular patient, compositions and mode of administration desired. The level of dose selected will depend on the activity of the particular peptide compound, the route of administration, the severity of the condition being treated and the condition of the patient's prior medical history that is being treated. treaty. However, it is within the skill in the art to start the doses of the peptide compound at levels lower than those necessary to obtain the desired therapeutic effect, and gradually increase the dose until the desired effect is achieved. In general, it is preferred for subcutaneous administration at dose levels of about 0.5 μg to 1,500 μg, levels of about 0.5 μg to 1,000 μg are more preferred, and what is most preferred are the levels of about 1 μg to 200 μg. For intrapulmonary delivery, preferred dose levels are about 0.5 μg to 10,000 μg, and most preferred, about 1 μg to 5,000 μg. In an especially preferred aspect, about 1 μg to 5,000 μg of the peptide compound of this invention is administered, once a day, to a mammalian patient, preferably subcutaneously or intrapulmonally.

IN VITRO AND IN VIVO PROOF PROCEDURES Compounds within the scope of this invention exhibit remarkable pharmacological activities in tests described in the literature, which are accepted in the art and recognized to correlate with pharmacological activity in humans and other mammals. The following in vivo and in vitro pharmacological tests are typical for characterizing the compounds of this invention. 1. - STIMULATION OF ADENYLATE CYCLASE IN CELLS ROS 17 / 2.8 The ability of the compounds of the invention to stimulate adenylate cyclase (AC) by the occupation of the PTH receptor is measured using a cAMP analysis in ROS 17 / 2.8 cells, as follows: Ros 17 cells are available in piacs. 2.8 to 1 x 105 cells / concavity in plates of 24 concavities. After 3-5 days the culture media is aspirated and replaced by 0.5 ml of the cAMP analysis buffer containing Ham's F12 medium, 2 mM IBMX, 1 mg / ml BSA, 35 mM HEPES and 20 μg / ml ascorbic acid. Balances the cells in the assay regulator by incubating the cells for 30 minutes at 37 ° C. Then the cAMP regulator is aspirated. The PTH analogs are diluted in the analyte regulator at various concentrations and added to the concavities. The cells are then incubated at 37 ° C for 20 minutes. After incubation, the cells are solubilized by adding 1% Triton. Total cAMP is measured using a flash proximity analysis discriminator system for cAMP (Amersham, Arlington Heights, IL, E.U.A.) and samples are counted using a Wallac microtiter plate flash counter. The data represent average cAMP values of duplicate samples + standard deviation (SD, acronym for its English designation: Standard Deviation). The EC50 values are defined as the concentration necessary to elicit the maximum mean stimulus and are calculated using a 4-parameter fit equation. 2. - AGGLUTINATION OF THE PTH RECEPTOR IN ROS CELLS 17 / 2.8 The competition of the compounds of the invention with PTH is measured to bind to the PTH receptor using the PTH receptor agglutination assay, which is described below. ROS 17 / 2.8 cells are plated as described for the cAMP analysis. After 3-5 days the culture media is aspirated and the cells are washed twice with 1 ml of binding buffer [50 mM Tris-HCl (pH 7.7), 100 mM NaCl, 2 mM CaCl2, 5 mM of KCl, 0.5% of HIFCS, 5% of horse serum Hl]. These cells are incubated with 100 pM of 125I- [Nle8"18, Tyr34] hPTH (1-34) NH2 (Amersham, Arlington Heights, IL, USA), both in the presence and in the absence of the unlabeled PTH analogue. incubate at 22 ° C for 2 hours the union is terminated by aspirating the regulator and washing the cells three times in cooled solution of analysis regulator.The radioactivity bound to cells is recovered by the addition of 0.1 N NaOH and counted using a counter Packard gamma rays The specific total binding was determined from the concavities that did not contain unlabeled peptide compound The data represent the average percentage of the total union of duplicate samples ± SD The Cl50 values for the competitive binding are calculated using a 4-parameter adjustment equation. 3. - STIMULATION OF ADENYLATE-CYCLASE IN CROPS PE CELLS PE SKULLS PE MOUSE AND PE RAT The response of cAMP in cultures of mouse and rat skull cells to the compounds of the invention is determined in the following manner. Osteoblast cells are isolated from fetal rat skulls (19-20 days of gestation) of skulls (days 1-2 of age) of neonatal mice. The frontal bone and parietal bone are isolated, cleaned of periosteum and loose connective tissue and cut with scissors. The digested skulls were then digested for 20 minutes in collagenase type 1 (0.1%) with 0.5% trypsin and 0.53 mM EDTA. The loosened cells of the digestion 4-7 are gathered, and they are washed until they are free of collagenase. The cells were plated at a concentration of 1 x 105 / ml in a-MEM with 10% FBS in plates of 24 concavities. The cells are equilibrated in assay regulator, incubating the cells for 30 minutes at 37 ° C. The cAMP regulator is then aspirated. Dilute various concentrations of the PTH peptide compounds in the analyte buffer and then add them. The cells are incubated at 37CC for 20 minutes. After incubation the cells are solubilized by adding 1% Triton. The total of cAMP is measured using a discriminant system for proximity, flash analysis for cAMP (Amersham, Arlington Heights, IL, E.U.A.) and the samples are counted using a flash counter for Wallac microtiter plate. The data represent the mean cAMP values of duplicate samples ± SD. The values are defined CE50 as the concentration necessary to provoke the maximum mean stimulus and are calculated using a 4-parameter fit equation. 4. - STIMULATION OF THE PRODUCTION OF cAMP IN RATS Female rats Harlan Spregue-Dawley (Lewis strain, 200 g) were anesthetized using a mixture of 70 mg / kg ketamine / 6 mg / kg xylazine. The peptide compound to be tested is then administered by the desired route (eg, intravenous, subcutaneous or intratracheal) in 1 ml / kg of phosphate-buffered saline vehicle. After one hour the urine is collected, either by urethral catheter or manually, applying gentle pressure on the area of the bladder. A blood sample is also collected by cardiac puncture. The urine sample is analyzed for cAMP levels using radioimmunoassay (Incstar, Stillwater, MN, E.U.A.), as described by Jaffé (Jaffé, M., Hoppe Seylers Z. Physiol. Chem., 1886, 10, 391). Serum and urine creatinine are also measured and creatinine levels are used to express cAMP levels as a function of glomerular filtration.

. - MEASUREMENT PE THE EFFECTS IN THE BONE PE RATAS Female rats from a retired breeder (Sprague-Dawley, 8-10 months of age) are subjected to bilateral ovarectomy. After two months of ovariectomy, treatment with a representative peptide compound is initiated. The peptide compound is prepared in phosphate-regulated isotonic saline, containing 2% heat-inactivated rat serum. The animals received daily subcutaneous injections (5 days / week) for four weeks. The day after the last treatment, bone mineral density throughout the body is measured by double-energy X-ray absorptiometry (DEXA, acronym for its English designation: Dual Energy X-ray Absorptiometry) to determine the degree of anabolic response. 6. - IN VITRO MEASUREMENT OF PTH ANTAGONIST ACTIVITY The antagonist activity of the compounds of the present invention is determined by measuring the output of cAMP using cultured mouse MC3T3-E1 osteoblasts, as described in. U.S. Patent No. 5,446,130, incorporated herein by reference. 7. - IN VIVO MEASUREMENT OF ACTIVIPAP ANTAGONIST PE PTH The in vivo effectiveness of the peptide compounds of this invention, such as PTH antagonists, is determined by measuring urinary phosphate and cAMP using normal procedures well known in the art, as valid measurements of PTH activity, as described in U.S. Pat. No. 4,423,037, incorporated herein by this reference.

LISTING PE SEQUENCES (1) GENERAL INFORMATION: (i) APPLICANT: Condom, Stephen M. Morize, Isabelle. (ii) TITLE OF THE INVENTION: PEPTIDE ANALOGS OF PARATHYROID HORMONE (iii) SEQUENCE NUMBER: 88 (iv) ADDRESS FOR CORRESPONDENCE: (A) RECIPIENT: Rhone-Pouienc Rorer, Inc. (B) STREET: 500 Areola Road, Mailstop 3C43 (C) CITY: Collegeville (D) STATE: PA (E) COUNTRY: USA (F) POSTAL CODE: 19426 (v) FORM THAT CAN BE READ IN COMPUTER: (A) TYPE OF MEDIA: Floppy disk (B) COMPUTER: PC compatible with IBM (C) OPERATING SYSTEM: PC-DOS / MS-DOS (D) PROGRAM: Patentln Edition # 1.0, version # 1.30 (vi) DATA OF THIS APPLICATION: (A) APPLICATION NO .: ( B) DATE OF PRESENTATION: (C) CLASSIFICATION: (vii) DATA FROM THE PRIOR APPLICATION: (A) APPLICATION NUMBER: US 60 / 046,472 (B) DATE OF SUBMISSION: May 14, 1997. (viii) EMPLOYEE / AGENT INFORMATION (A) NAME: Michael B. Martin, attorney (B) REGISTRATION NUMBER: 37,521 (C) REFERENCE CASE NUMBER: A2678B-WO (ix) TELECOMMUNICATIONS INFORMATION (A) PHONE: (610) 454-2793 (B) TELEFAX : (610) 454-3808 (2) INFORMATION FOR SEQ ID NO: 1: (i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 34 amino acids (B) TYPE: amino acid (C) No. OF FILAMENTS: (D) TOPOLOGY: irrelevant, (ii) TYPE OF MOLECULE: Peptide. (v) TYPE OF FRAGMENT: N-terminal (xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 1: Ser Val Ser Glu He Gln Leu Met His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Met Glu Arg Val Glu Trp Leu Arg Lys Lys Leu Gln Asp Val His 20 25 30 Asn Phe. (2) INFORMATION FOR SEQ ID NO: 2: (i) CHARACTERISTICS OF THE SEQUENCE: (A) LENGTH: 34 amino acids (B) TYPE: amino acid (C) No. OF FILAMENTS: (D) TOPOLOGY: irrelevant, (ii) TYPE OF MOLECULE: Peptide. (v) FRAGMENT TYPE: N-terminal (xi) DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 2: Val Ser Glu Wing His Gln Leu Leu His Asp Lys Gly Lys Ser He Gln 1 5 10 15 Asp Leu Arg Arg Arg Phe Phe Leu His His Leu He Wing Glu lie His 20 25 30 Thr Ala (2) .- INFORMATION FOR SEQ ID NO: 3 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (¡x) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) ) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This amino acid C-termini is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 3: Wing Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 4 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "This sequence has a C-terminus of amide (ie CONH2), instead of a carboxy C-terminus (ie, COOH)". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 4: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 5 (i) .- CHARACTEROSTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nle" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (X) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 5: Ala Ala Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 6 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2'7 (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 6: Ala Ala Ala Gllu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 7 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 7: Ala Val Ser Ala He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu GIn Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 8 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 8: Ala Val Ser Glu Ala Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 9 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminai (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This amino acid C-terminai is a amide, that is, CONH2'7 (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 9: Ala Val Ser Glu He Ala Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 10 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nle" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 10: Ala Val Ser Glu lie GIn Ala Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 1 1 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This amino acid C-termini is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 1 1: Ala Val Ser Glu He GIn Leu Xaa Ala Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 12 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids - (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (i) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminai (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2'7 (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 12: Ala Val Ser Glu He GIn Leu Xaa His Wing Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 13 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) 7 - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 13: Wing Val Ser Glu He Gln Leu Xaa His Asn Wing Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 14 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 14: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Ala Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 15 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminai (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 15: Ala Vai Ser Glu lie Gln Leu Xaa His Asn Leu Gly Ala His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 16 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 16: Ala Val Ser Glu Lie Gln Leu Xaa His Asn Leu Gly Lys Ala Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 17 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 17: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Wing Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 18 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminai (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product =" Nie "(ix) ) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This amino acid C-termini is an amide, that is, CONH2'7 (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 18: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Ala 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 19 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 19: Wing Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ala Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 20 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 20: Gly Val Ser Glu lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 21 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" '/ note = "This C-terminal amino acid is an amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 21: Wing Gly Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 22 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid 5 (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: 10 (A) .- NAME / KEY: Peptide (B) ) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide 15 (B) .- LOCATION: 18 ... 22 - • (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The lateral chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature", (ix) .- ASPECT: 20"(A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note =" This amino acid C - terminal is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 22: Wing Val Gly Glu Lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 23 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (¡x) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 23: Ala Val Ser Gly lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 24 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (i) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 24: Ala Val Ser Glu Gly Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 25 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 25: Wing Val Ser Glu He Gly Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 26 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 26: Ala Val Ser Glu He Gln Gly Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 27 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (i) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 27: Ala Val Ser Glu He Gln Leu Gly His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 28 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) ) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 28: Ala Val Ser Glu He Gln Leu Xaa Gly Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 29 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2" (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 29: Wing Val Ser Glu He Gln Leu Xaa His Gly Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu GIn Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 30 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF SEQUENCE: SEQ ID NO: 30: Ala Val Ser Glu ile Gln Leu Xaa His Asn Gly Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 31 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (I) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) ) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 31: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Gly His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 32 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 32: Wing Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys Gly Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 33: (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) ) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 33: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Gly Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 34 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide ( B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 34: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu GÍy Lys His Leu Gly 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 35 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix). - ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in the position 18 and Asp in position 22 are linked by an amide ligature ", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is an amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 35: Wing Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Gly Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 36 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 1 (D) .- OTHER INFORMATION: / product = "OTHER". / note = "Xaa in position 1 is D-proinin". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION : / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF SEQUENCE: SEQ ID NO: 36: Xaa Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 37 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 3 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "Ei Xaa in position 3 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2" (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 37: Ala Val Xaa Glu Lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 38 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 6 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The Xaa in position 6 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide ( B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This amino acid C-termini is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 38: Ala Val Ser Glu He Xaa Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 39 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 7 (D) .- OTHER INFORMATION: / product = "OTHER" / note = " Xaa in position 7 is D-proinin. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature ", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2" (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 39: -Ala Val Ser Glu Lie Gln Xaa Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 40 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 9 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "Xaa in position 9 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature ". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 40: Ala Val Ser Glu He Gln Leu Xaa Xaa Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 41 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 10 (D) .- OTHER INFORMATION : / product = "OTHER" / note = "The Xaa in position 10 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 41: Wing Val Ser Glu He Gln Leu Xaa His Xaa Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 42 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: -10 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT:. (A) .- NAME / KEY: Peptide (B) .- LOCATION: -4 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "Xaa in position 14 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 1 ... 5 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature, and this sequence has a C amide end (ie, CONH2) instead of a carboxy C-terminus (i.e.

COOH). "(Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 42: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys Xaa Leu Asn -15 -10 -5 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu GIn Asp Val 1 5 10 (2) .- INFORMATION FOR SEQ ID NO: 43 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 15 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The Xaa in position 15 is D-proinin. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2" (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 43: Wing Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Xaa Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 44 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 16 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "Xaa in position 16 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 44: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Xaa 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 45 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 17 (D) .- OTHER INFORMATION : / product = "OTHER" / note = "The Xaa at position 17 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2" (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 45: Wing Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Xaa Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 46 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 34 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION : / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 34 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 46: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val His 20 25 30 Asn Phe (2) .- INFORMATION FOR SEQ ID NO: 47 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nle" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) 7- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 47: Wing Val Ser Glu He GIn Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Be Asp Glu Arg Val Lys Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 48 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 (D) .- OTHER INFORMATION : / product = "Orn" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Orn in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 48: Ala Val Ser Glu lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Xaa Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 49 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 22 (D) .- ANOTHER INFORMATION: / product = "Orn" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER "/ note =" The side chains of Lys in position 18 and Orn in position 22 are linked by an amide ligature ", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 49: Wing Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Be Asp Glu Arg Val Xaa Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 50 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Glu in position 22 are linked by an amide ligature". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 50: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Glu Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 51 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 1 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide ( B) .- LOCATION: 1 1 (D) .- OTHER INFORMATION: / product = "Orn" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 1 1 .. .15 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Orn in position 18 and Glu in position 22 are linked by an amide ligature", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 24 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is an amide, that is, CONH (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 51: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn -5 1 5 Ser Xaa Glu Arg Val Glu Trp Leu Arg Lys Leu Leu Gln Asp Val 10 15 20 (2) .- INFORMATION FOR SEQ ID NO: 52 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 30 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 30 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2" (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 52: Ala Val Ser Glu lie GIn Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 53 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 29 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irreventent (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 29 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 53: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln 20 25 (2) .- INFORMATION FOR SEQ ID NO: 54 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 28 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 28 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 54: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu 20 25 (2) .- INFORMATION FOR SEQ ID NO: 55 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 27 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 27 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 55: Ala Val Ser Glu Lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu 20 25 (2).- INFORMATION FOR SEQ ID NO: 56 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 22 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY : Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 9. ..13 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The lateral chains of Lys in position 9 and Asp in position 13 are linked by an amide ligature", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 22 (D) .- Other information: / product = "OTHER" / note = "This amino acid C-termini is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 56: Asn Leu Gly Lys His Leu Asn Ser Lys Glu Arg Val Asp Trp Leu Arg 1 5 10 15 Lys Leu Leu Gln Asp Val 20 (2) .- INFORMATION FOR SEQ ID NO: 57 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 23 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 10 ... 14 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 10 and Asp in position 14 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 23 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2." (Xi) .- DESCRIPTION OF SEQUENCE: SEQ ID NO: 57: His Asn Leu Gly Lys His Leu Asn Ser Lys Glu Arg Val Asp Trp Leu 1 5 10 15 Arg Lys Leu Leu Gln Asp Val 20 (2) .- INFORMATION FOR SEQ ID NO: 58 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 24 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 1 1 ... 15 (D) .- OTHER INFORMATION: / product = "OTHER "/ note =" The side chains of Lys in position 11 and Asp in position are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 24 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 58: Xaa His Asn Leu Gly Lys His Leu Asn Ser Lys Glu Arg Val Asp Trp 1 5 10 15 Leu Arg Lys Leu Leu Gln Asp Val 20 (2) .- INFORMATION FOR SEQ ID NO: 59 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 25 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 2 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 12 ... 16 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 12 and Asp in position 16 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 25 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 59: Leu Xaa His Asn Leu Gly Lys His Leu Asn Ser Lys Glu Arg Val Asp 1 5 10 15 Trp Leu Arg Lys Leu Leu GIn Asp Val 20 25 (2) .- INFORMATION FOR SEQ ID NO: 60 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 26 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 3 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 13 ... 17 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 13 and Asp in position 17 are linked by an amide ligature", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 26 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 60: Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn Ser Lys Glu Arg Val 1 5 10 15 Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 (2) .- INFORMATION FOR SEQ ID NO: 61 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 27 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 4 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 14 ... 18 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 14 and Asp at position 18 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 27 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 61: He Gin Leu Xaa His Asn Leu Gly Lys His Leu Asn Ser Lys Glu Arg 1 5 10 15 Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 (2) .- INFORMATION FOR SEQ ID NO: 62 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 28 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 5 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 15 ... 19 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 15 and Asp in position 19 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 28 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF SEQUENCE: SEQ ID NO: 62: Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn Ser Lys Glu 1 5 10 15 Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 (2) .- INFORMATION FOR SEQ ID NO: 63 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 29 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 6 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 16 ... 20 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 16 and Asp in position are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 29 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 63: Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn Ser Lys 1 5 10 15 Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 (2) .- INFORMATION FOR SEQ ID NO: 64 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 30 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 7 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 17 ... 21 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 17 and Asp in position 21 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 30 (D). - _ Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF SEQUENCE: SEQ ID NO: 64: Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn Ser 1 5 10 15 Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 65 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 28 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 2 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 12 ... 16 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 12 and Asp in position 16 are linked by an amide ligature ". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 28 1 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 65: Leu Xaa His Asn Leu Gly Lys His Leu Asn Ser Lys Glu Arg Val Asp 1 5 10 15 Trp Leu Arg Lys Leu Leu Gln Asp Val His Asn Phe 20 25 (2) .- INFORMATION FOR SEQ ID NO: 66 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 (D) .- OTHER INFORMATION : / PRODUCT = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 10 ... 14 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 10 and Asp in position 14 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2" . (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 66: Wing Val Ser Glu Lie Gln Leu Xaa His Lys Leu Gly Lys Asp Leu Asn 1 5 10 15 Ser Xaa Glu Arg Val Glu Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 67 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 14 ... 18 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 14 and Asp in position 18 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 67: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys Lys Leu Asn 1 5 10 15 Being Asp Glu Arg Val Glu Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 68 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 (D) .- ANOTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 17 ... 21 (D) .- OTHER INFORMATION: / product = "OTHER "/ note =" The side chains of Lys in position 17 and Asp in position 21 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 68: Wing Val Ser Glu He GIn Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Lys Xaa Glu Arg Asp Glu Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 69 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 (D) .- OTHER INFORMATION : / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 21 ... 25 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 21 and Asp in position 25 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 69: Ala Val Ser Glu He GIn Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Xaa Glu Arg Lys Glu Trp Leu Asp Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 70 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 25 ... 29 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 25 and Asp in position 29 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2." (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 70: Ala Val Ser Glu Lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Xaa Glu Arg Val Glu Trp Leu Lys Lys Leu Leu Asp Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 71 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 34 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The lateral chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature", ( ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 34 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 71: Wing Val Ser Glu His Gln Leu Leu His Asp Lys Gly Lys Ser He Gln 1 5 10 15 Asp Lys Arg Arg Arg Asp Phe Leu His His Leu He Wing Glu He His 20 25 30 Thr Ala (2) .- INFORMATION FOR SEQ ID NO: 72 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 34 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 34 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 72: Ala Val Ser Glu His Gln Leu Leu His Asp Lys Gly Lys Ser lie Gln 1 5 10 15 Asp Lys Arg Arg Arg Asp Leu Leu Glu Lys Leu Leu Glu Lys Leu His 20 25 30 Thr Ala (2) .- INFORMATION FOR SEQ ID NO: 73 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 13 ... 17 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 13 and Asp in position 17 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product =" OTHER "/ note =" The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 73: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 • Asp Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Vai 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 74 (i) .- CHARACTERISTICS OF THE SEQUENCE: 10 (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide 15 (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) ) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" 20 (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 26 ... 30 (D) .- OTHER INFORMATION: / product =" OTHER "/ note =" The side chains of Lys in position 26 and Asp in position are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 74: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 75 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 34 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: (D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix). - ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 13 ... 17 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The lateral chains of Lys in the position 13 and Asp in the position 17 are linked by an amide ligature. "(¡X) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 34 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2" . (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 75: Ala Val Ser Glu Lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Asp Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val His 20 25 30 Asn Phe (2) .- INFORMATION FOR SEQ ID NO: 76 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 13 ... 17 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 13 and Asp in position 17 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 26 ... 30 (D) .- OTHER INFORMATION: / product =" OTHER "/ note =" The side chains of Lys in position 26 and Asp in position are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 76: Ala Val Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Asp Xaa Glu Arg Val Glu Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 77 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 28 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 12 ... 16 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The lateral chains of Lys in position 12 and Asp in position 16 are linked by an amide ligature", ( ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 28 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 77: Leu Leu His Asp Lys Gly Lys Ser He Gln Asp Lys Arg Arg Arg Asp 1 5 10 15 Phe Leu His His Leu He Wing Glu lie His Thr Wing 20 25 (2) .- INFORMATION FOR SEQ ID NO: 78 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 28 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 2 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 7 ... 11 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The lateral chains of Lys in position 7 and Asp in position 1 1 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 12 ... 16 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 12 and Asp in position 16 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 28 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 78: Leu Xaa His Asn Leu Gly Lys His Leu Asn Asp Lys Glu Arg Val Asp 1 5 10 15 Trp Leu Arg Lys Leu Leu Gln Asp Val His Asn Phe 20 25 (2) .- INFORMATION FOR SEQ ID NO: 79 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 28 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D). ~ TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 2 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 12 ... 16 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 12 and Asp in position 16 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 20 ... 24 (D) .- OTHER INFORMATION: / product =" OTHER" / note = "The side chains of Lys in position 20 and Asp in position 24 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 28 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 79: Leu Xaa His Asn Leu Gly Lys His Leu Asn Ser Lys Glu Arg Val Asp 1 5 10 15 Trp Leu Arg Lys Leu Leu Gln Asp Val His Asn Phe 20 25 (2) .- INFORMATION FOR SEQ ID NO: 80 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-termini (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide ( B) .- LOCATION: 13 ... 17 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The lateral chains of Lys in position 13 and Asp in position 17 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product =" OTHER "/ note =" The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 26 ... 30 (D) .- OTHER INFORMATION: / Product = "OTHER" / note = "The side chains of Lys in position 26 and Asp in position are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 80: Ala Val Ser Glu Lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Asp Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 81 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 81: Ala Val Ser Glu lie Gln Leu Ala His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 82 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 2 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The Xaa in position 2 is D-proline. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 82: Ala Xaa Ser Glu He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 25 30 (2) .- INFORMATION FOR SEQ ID NO: 83 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 4 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The Xaa in position 4 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The lateral chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature", (ix) .- ASPECT: (A ) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This amino acid C-termini is an amide, that is, CONH2". (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 83: Val Ser Xaa He Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 84 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (i) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 5 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The Xaa in position 5 is D-proline. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A). - NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature ", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is an amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 84: Ala Val Ser Glu Xaa Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 85 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The Xaa in position 8 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature ", (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C-terminal amino acid is an amide, that is, CONH2" . (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 85: Ala Val Ser Glu Lie Gln Leu Xaa His Asn Leu Gly Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu GIn Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 86 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION 1 1 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The Xaa in position 11 is D-proline "(x) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product =" OTHER "/ note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 86: Ala Val Ser Glu lie GIn Leu Xaa His Asn Xaa Gly Lys His Leu Asn 1 5 10 '15 Ser Lys Giu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 87 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (i) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 12 (D) .- ANOTHER INFORMATION: / product = "OTHER" / note = "The Xaa in position 12 is D-proline" (¡x) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18. ..22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. " (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product = "OTHER" / note = "This C - terminal amino acid is a amide, that is, CONH2. " (xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 87: Wing Val Ser Glu He Gln Leu Xaa His Asn Leu Xaa Lys His Leu Asn 1 5 10 15 Ser Lys Glu Arg Val Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30 (2) .- INFORMATION FOR SEQ ID NO: 88 (i) .- CHARACTERISTICS OF THE SEQUENCE: (A) .- LENGTH: 31 amino acids (B) .- TYPE: amino acid (C) .- No. OF FILAMENTS: ( D) .- TOPOLOGY: Irrelevant (ii) .- TYPE OF MOLECULE: Peptide (v) .- TYPE OF FRAGMENT: N-terminal (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B). - LOCATION: 8 (D) .- OTHER INFORMATION: / product = "Nie" (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 13 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "Xaa in position 13 is D-proline". (ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 18 ... 22 (D) .- OTHER INFORMATION: / product = "OTHER" / note = "The side chains of Lys in position 18 and Asp in position 22 are linked by an amide ligature. "(Ix) .- ASPECT: (A) .- NAME / KEY: Peptide (B) .- LOCATION: 31 (D) .- Other information: / product =" OTHER "/ note = "This C-terminal amino acid is an amide, that is, CONH2". (Xi) .- DESCRIPTION OF THE SEQUENCE: SEQ ID NO: 88: Ala Val Ser Glu lie Gln Leu Xaa His Asn Leu Gly Xaa His Leu Asn 1 5 10 15 Ser Lys Glu Arg Vai Asp Trp Leu Arg Lys Leu Leu Gln Asp Val 20 25 30

Claims

NOVEDAP PE THE INVENTION CLAIMS • 5 1. A cyclic peptide compound of the formula: X-A? 0-A? 1 -Ai 2-A? 3-A14-A? 5-A16-A? 7-A? 8-A? 9-A20-A2? -A22-A23-A24-A25-A26-A27-Y or a pharmaceutically acceptable salt or prodrug thereof; in which X is selected from the group consisting of: (a) R a-Ao-Ai ^ -As-t-As-Ae-A? - A8-A9-, (b) Ria-A? .- As- As-Ae-A '-As-Ag-, (c) (d) R a- 10 AtAs-Ae-ArAs-Ag-, (e) Ria-As-Ae-A s-Ag-, a-A7-A8- Ag-, (h) Ria-As-Ag-, (i) R a-Ag- and 0) R a-; And it is selected from the group consisting of: (a) -R3, (b) -A28-R3, (c) -A28-A29-R3, (d) -A28-A29-A3o-R3, (e) -A28 - A29-A3o-A3i-R3, (f) -A28-A29-A3o-A3? -A32 -R3, (g) -A28-A29-A30-A3? -A32-A33 -R3, and (h) - A28-A29-A30-A31-A32-A33-A34-R3; is H, alkyl, aralkyl or -COR2; i 15 is R? A or a group of the formula: R2 is alkyl, alkenyl, alkynyl, aryl or aralkyl; R3 is a group of formula A35-OR or Ass-NR ^; l ^ and R5 are independently H or lower alkyl; R6 and Rg are independently H or alkyl; R7 is alkyl; R8 is H, alkyl or COR2; R10 is H or halogen; Rn is alkyl or aralkyl; m is 1, 2 or 3; n is 3 or 4; A0 is absent or is a peptide of 1 to 6 amino acid residues; Ai is Ser, Ala, Gly or D-Pro, or an amino acid equivalent to them; A2 is Ala, Val or Gly, or an equivalent amino acid of them; A3 is Ala, Ser, Gly or D-Pro, or an amino acid equivalent to them; At is Glu, Ala or Gly, or an equivalent amino acid thereof; A5 is Lie, His, Ala or Gly, or an amino acid equivalent to them; Aß is Ala, Gln, Gly or D-Pro, or an amino acid equivalent to them; A is Ala, Leu, Gly or an amino acid equivalent to them; A8 is Leu, Nie, Gly or D-Pro, or an amino acid equivalent thereof; Ag is His, Ala, D-Pro or Gly, or an amino acid equivalent thereof; A10 is Ala, Asn, Asp, Cys, homo-Cys, Glu, Gly, Lys, Orn, Ser, Thr, D-Pro, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; An is Ala, Gly, Leu or Lys or an equivalent amino acid thereof; A? 2 is Ala or Gly, or an equivalent amino acid thereof; A13 is Ala, Asn, Asp, Cys, homo-Cys, Glu, Gly, Lys, Orn, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; Au is Ala, Asn, Asp, Cys, homo-Cys, Glu, Gly, His, Lys, Orn, Ser, Thr, D-Pro, -NHCH (CH2) mNH2) CO- or - NHCH [(CH2) pC02H] CO-; A? 5 is Ala, Gly, He, D-Pro or Leu, or an equivalent amino acid thereof; A? 6 is Asn, Ala, Gly, D-Pro or Gln or an equivalent amino acid thereof; A? 7 is Ala, Asn, Asp, Cys, homo-Cys, Glu, Gly, Lys, Orn, Ser, Thr, D-Pro, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; Ais is Asp, Cys, homo-Cys, Glu, His, Leu, Lys, Orn, Nie, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; Ai9 is Arg or Glu or an amino acid equivalent to them; A2o is Arg or an equivalent amino acid thereof; A2? is Arg, Asp, Cys, homo-Cys, Glu, Lys, Orn, Ser, Thr, Val, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; A22 is Asp, Cys, homo- Cys, Glu, His, Lys, Orn, Phe, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CH-; A23 is Leu, Phe or Trp, or an amino acid equivalent to them; A24 is Leu or an equivalent amino acid thereof; A25 is Arg, Asp, Cys, homo-Cys, Glu, His, Lys, Orn, D-Pro, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; A26 is Asp, Cys, homo-Cys, Glu, His, Lys, Orn, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; A27 is Leu or Lys, or an amino acid equivalent to them; A28 is He or Leu or an amino acid equivalent to them; A2 is Ala, Asp, Cys, homo-Cys, Glu, Gln, Lys, Orn, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; A30 is Asp, Cys, homo-Cys, Glu, Gly, Lys, Orn, Ser, Thr, -NHCH (CH2) mNH2) CO- or -NHCH [(CH2) nC02H] CO-; A31 is He, Leu or Val or an amino acid equivalent to them; A32 is His or an equivalent amino acid thereof; A33 is Asn or Thr, or an amino acid equivalent to it; and A3 is Ala or Phe, or an amino acid equivalent thereto; A35 is absent or is a peptide of 1 to 4 amino acids; and the side chains of at least one of the following pairs of amino acid residues A10 and Au, A13 and A? 7, A and A? 8, Au and A2 ?, A? 8 and A22, A2i and A25, A25 and A2g and A26 and A30 are linked by means of an amide, ester, disulfide or lanthionine bond to form a bridge; and the side chain of each of the following amino acid residues: A10, A13, Au, A? 7, A? 8, A2? A22, A25, A2?, A2g and A30 contributes, at most, to the formation of a single bridge; provided that, when the side chains of the following pairs of amino acid residues, A13 and A? or A26 and A30 are linked through an amide bond, disulfide or lanthionine, to form a bridge; then the side chains of at least one of the following pairs of amino acid residues, A10 and Au, Au and A18, A17 and A2i, A? 8 and A22, A2? and A25 and A25 and A2g are also linked through an amide, ester, disulfide or lanthionine ligature.
2. A peptide compound according to the claim 1, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that the bridge formed from the side chains of a pair of amino acid residues is non-overlapping with a bridge formed between the side chains of another pair of amino acid residues.
3. A peptide compound according to the claim 2, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A? 0 is Ala, Asn, Asp, Gly or Lys; A? 3 is Ala, Gly or Lys; Au is Ala, Asp, Gly, His, Lys or Ser; TO? is Ala, Asp, Gly, Lys or Ser; A? 8 is Asp, Leu, Lys, Orn or Nie; A2? is Arg, Asp, Lys or Val; A22 is Asp, Glu, Lys, Orn or Phe; A25 is Arg, Asp, Glu, His or Lys; A26 is His or Lys; A2g is Ala, Asp, Glu or GIn; A30 is Asp, Glu or Lys; and the side chains of at least one of the following pairs of amino acid residues: A10 and Au, A? 3 and A? , Au and Ais, A17 and A2 ?, Ais and A22, A2i and A25, A25 and A29 and A26 and A30 are linked by means of an amide ligature to form a bridge; and the side chain of each of A 0, A? 3, A, A? 7, A? 8, A2 ?, A22, A25, A26, A2g and A30 contribute, at most, to the formation of a single bridge; provided that: (a) when the side chains of A? 3 and A? they are linked by means of a ligature amide to form a bridge, the side chains of at least one of A s and A22, A2? and A25 and A25 and A29 are also linked by means of an amide ligature; (b) when the side chains of A2ß and A30 are linked by means of an amide bond to form a bridge, the side chains of at least one of A10 and Au, Au and Ais, A? 7 and A2 ?, A? 8 and A22 and A2? and A25, are also linked by means of an amide ligature; and (c) when the side chains of A? 3 and A? 7 and A26 and A30 are linked by means of an amide bond to form a bridge, the side chains of Ais and A22 or A2? and A25 are also linked through an amide ligature.
4. A peptide compound according to the claim 3, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that R a is H and Y is NH 2.
5. A peptide compound according to the claim 4, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that X is (a) (b) 6. - A peptide compound according to the claim 5, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A is Ala, Gly or D-Pro; A8 is Nie and A27 is Leu. 7. A peptide compound according to the claim 6, or a salt or. pharmaceutically acceptable prodrug thereof, further characterized in that; (i) the side chains of A 0 and Au are linked by means of an amide bond to form a bridge; (ii) the side chains of A and A? 8 are linked by means of an amide ligature to form a bridge; (iii) the side chains of A 7 and A21 are linked by means of an amide ligature to form a bridge; (iv) the side chains of A? 8 and A22 are linked by means of an amide bond to form a bridge; (v) the side chains of A2? and A25 are linked by means of an amide ligature to form a bridge; (vi) the side chains of A25 and A2g are linked by means of an amide ligature to form a bridge. 8. A peptide compound according to claim 7, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A? 0 is Asp or Lys; A 3 is Lys; Au is Asp or Lys; A? 7 is Asp or Ser; A 8 is Nie; A2? is Arg or Val; A22 is Glu or Phe; A25 is Arg or His; A2ß is Lys or His; A2g is Ala or Gln; and A3o is Asp or Glu; and the side chains of A 0 and Au are linked by means of an amide bond to form a bridge. 9. A peptide compound according to claim 7, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A10 is Asn or Asp; A13 is Lys; Au is Asp or Lys; A? T- is Asp or Ser; Ais is Nie; A2? is Arg or Val; A22 is Glu or Phe; A25 is Arg or His; A26 is His or Lys; A2g is Aia or Gln; and A30 is Asp or Glu; and the side chains of Au and Ais are linked by means of an amide ligature to form a bridge. 10. - A peptide compound according to claim 7, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A10 is Asn or Asp; A13 is Lys; Au is His or Ser; A? 7 is Asp or Lys; A? 8 is Nie; A2 is Asp or Lys; A22 is Glu or Phe; A25 is Arg or His; A26 is His or Lys; A2g is Ala or Gln; and A30 is Asp or Glu; and the side chains of A17 and A2? they are linked by means of an amide ligature to form a bridge. 1. A peptide compound according to claim 7, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A10 is Asn or Asp, A13 is Lys; Au is His or Ser; A17 is Asp or Ser; A? 8 is Asp, Lys or Orn; A2? is Arg or Val; A22 is Asp, Glu, Lys or Orn; A25 is Arg or His; A26 is His or Lys; A2g is Ala or GIn; and A30 is Asp or Glu; and the side chains of Ais and A22 are linked by means of an amide ligature to form a bridge. 12. A peptide compound according to claim 7, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A10 is Asn or Asp; A 3 is Lys; A is His or Ser; A is Asp or Ser; A? 8 is Nie; A21 is Asp or Lys; A22 is Glu or Phe; A25 is Asp or Lys; A26 is His or Lys; A2g is Ala or GIn; and A3o is Asp or Glu; and the side chains of A2 and A25 are linked by means of an amide ligature to form a bridge. 13. A peptide compound according to claim 7, or a pharmaceutically acceptable salt or prodrug of the same, further characterized in that A10 is Asn or Asp; A? 3 is Lys; A14 is His or Ser; A? 7 is Asp or Ser; A? 8 is Nie; A21 is Arg or Val; A22 is Glu or Phe; A25 is Asp or Lys; A2ß is His or Lys; A2g is Asp or Lys; and A30 is Asp or Glu; and the side chains of A25 and A2g are linked by means of an amide ligature to form a bridge. 14. A peptide compound according to claim 6, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that (i) the side chains of A13 and A? they are linked by means of an amide bond and the side chains of A 8 and A22 are linked by means of an amide bond, to form a bridge; and (ii) the side chains of A? 8 and A22 are linked by means of an amide bond, and the side chains of A2T and A30 are linked by means of an amide bond to form a bridge. 15. A peptide compound according to claim 14, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A10 is Asn or Asp; A13 is Lys or Asp; Au is His or Ser; A17 is Lys or Asp; A? 8 is Lys or Asp; A21 is Val or Arg; A22 is Glu, Lys or Asp; A25 is Arg or His; A2ß is Lys or Asp; A2g is Ala or Gln; and A30 is Lys or Asp; and the side chains of A 3 and A 7 are linked by means of an amide bond, and the side chains of A 8 and A 22 are linked by means of an amide bond to form a bridge. 16. A peptide compound according to claim 14, or a pharmaceutically acceptable salt or prodrug of the same, further characterized in that A10 is Asn or Asp; A13 is Lys; Au is His or Ser; A? 7 is Ser or Asp; A? 8 is Lys or Asp; A21 is Val or Arg; A22 is Glu, Lys or Asp; A25 is Arg or His; A26 is Lys or Asp; A29 is Ala or Gln; and A30 is Lys or Asp; and the side chains of Aβ8 and A22 are linked by means of an amide linkage and the side chains of A26 and A30 are linked by means of an amide linkage to form a bridge. 17. A peptide compound according to claim 6, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that the side chains of A13 and A? they are linked by means of an amide bond and the side chains of Ais and A22 are linked by means of an amide bond, and the side chains of A26 and A3o are linked by means of an amide bond to form a bridge. 18. A peptide compound according to claim 17, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A 0 is Asn or Asp; A? 3 is Lys or Asp; Au is His or Ser; TO? is Lys or Asp; A? 8 is Lys or Asp; A2? is Val or Arg; A22 is Glu, Lys or Asp; A25 is Arg or His; A26 is Lys or Asp; A29 is Ala or Gln; and A30 is Lys or Asp. 19. A peptide compound according to claim 1, further characterized in that it is selected from: Cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 3) ) cycle (K18- D ^) [A1, ¿, NleB, K1B, D ^, L 1hPTH (1-31) NH2 (SEQ ID NO: 5) cycle (K 18) D22) [A1'3, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 6) cycle (K18-D22) [A1'4, Nle8, K8, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 7) Cycle (K18-D22) [A1'5, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 8) Cycle (K18- D22) [A1-d, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 9) cycle (K18-D22) [A1'7, Nle8, K18, D22, L27] hPTH ( 1-31) NH2 (SEQ ID NO: 10) cycle (K18-D22) [Ar9, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 11) cycle (K18-D22) [ A1'10, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 12) cycle (K18-D22) [A1'11, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 13) Cycle (K18-D22) [A112, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 14) Cycle (K18-D22) [A1 ' 13, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 15) cycle (K18-D22) [A1'14, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 16) cycle (K18-D22) [A1'15, Nle8, K8, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 17) cycle (K18-D22) [A1 ' 16, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 18) cycle (K18-D22) [A1'17, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 19) cycle (K18-D22) [G1, Nle8, K18, D22, L27] hPTH (1- 31) NH2 (SEQ ID NO: 20) cycle (K18-D22) [A1, G2, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 21) cycle (K18-D22) [ A1, G3, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 22) cycle (K18-D22) [A1, G4, Nle8, K18, D22, L27] hPTH (1-31) ) NH2 (SEQ ID NO: 23) Cycle (K18-D22) [A1, G5, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 24) Cycle (K18-D22) [A1 , G6, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 25) cycle (K18-D22) [A1, G7, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 26) Cycle (K18-D22) [A1, G8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 27) Cycle (K18-D22) [A1, G9, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 28) cycle (K18- D ^) [A \ Glu, NleB, K1B, D L ^] hPTH (1-31) NH2 (SEQ ID NO: 29) cycle (K 18 D22) [A1, G11, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 30) cycle (K18-D22) [A1, G13, Nle8, K18, D22, L27] hPTH ( 1-31) NH2 (SEQ ID NO: 31) cycle (K18-D22) [A1, G14, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 32) cycle (K18-D22) ) [A1, G15, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 33) cycle (K18-D22) [A1, G16, Nle8, K18, D22, L27] hPTH (1 -31) NH2 (SEQ ID NO: 34) cycle (K18-D22) [A1, G7, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 35) cycle (K18-D22) ) [D-P1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 36) cycle (K18-D22) [A1, D-P3, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 37); cycle (K18-D22) [A1, D-P6, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 38); Cyclo (K18-D22) [A1, D-P7, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 39); cycle (K18-D22) [A1, D-P9, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 40); cycle (K18-D22) [A1, D-P10, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 41); cycle (K18-D22) [A1, D-P14, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 42); cyclo (K18-D22) [A1, D-P15, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 43); cicio (K18-D22) [A1, D-P6, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 44); cycle (K18-D22) [A1, D-P17, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 45); cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-34) NH2 (SEQ ID NO: 46); cycle (D18-K22) [A1, Nle8, D18, K22, L27] hPTH (1-31) NH2 (SEQ ID NO: 47); cycle (018-D22) [A1, Nle8.018, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 48); Cyclo (D18-O22) [A1, Nie8, D18, O22, L27] hPTH (1-31) NH2 (SEQ ID NO: 49); cycle (K18-E22) [A1, Nle8, K18, E22, L27] hPTH (1-31) NH2 (SEQ ID NO: 50); cycle (O18-E22) [A1, Nle8.018, E22, L27] hPTH (1-31) NH2 (SEQ ID NO: 51); cycle (K18- D22) [A1, Nle8, K18, D22, L27] hPTH (1-30) NH2 (SEQ ID NO: 52) cycle (K18-D22) [A1, NIe8, K18, D22, L27] hPTH (1-29) NH2 (SEQ ID NO: 53): cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-28) NH2 (SEQ ID NO: 54) cycle (K18-D22) [A1, Nle8 , K18, D22, L27] hPTH (1-27) NH2 (SEQ ID NO: 55) cycle (K18- ) NH2 (SEQ ID NO: 63) cicio (K18-, 8? X18 rv22, 27 10 D ^) [NleB, K1B, D ^, L ''] hPTH (2-31) NH2 (SEQ ID NO: 64); cycle (K D14) [A, Nle8'18, K10, D14, L27] hPTH (1-31) NH2 (SEQ ID NO: 66) cycle (K14-D18) [A1, Nie8, K4, D18, L27] hPTH (1-31) NH2 (SEQ ID NO: 67) cycle (K17-D21) [A1, Nle8'18, K17, D21 > L27] hPTH (1-31) NH2 (SEQ ID NO: 68) cycle (K21-D25) [A1, Nle8'18, K2, D25, L27] hPTH (1-31) NH2 (SEQ ID NO: 69) cycle (K25-D29) [A1, Nle8'18, K25, D29, L27] hPTH (1-31) NH2 (SEQ ID NO: 70) cycle (K18-D22) [K18, D22] hPTHrP (1-34) NH2 (SEQ ID NO: 71); cycle (K18-D22) [K18'26.30, D22, L23-28'31, E25'29] hPTHrP (1-34) NH2 (SEQ ID NO: 72); bicicio (K13-D17, K18-D22) [A1, Nle8, D17'22, K18, L27] hPTH (1-31) NH2 (SEQ ID NO: 73); bicyclo (K18-D22, K26-D30) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 74) and tricycle (K13-D17, K18-D22, K26-D30) [A1 > Nle8, K18, D17'22, L27] hPTH (1-31) NH2 (SEQ ID NO: 80); or a pharmaceutically acceptable salt or prodrug thereof. 20. A peptide compound according to claim 1, further characterized in that it is selected from: Cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 3) ) cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-34) NH2 (SEQ ID NO: 46) cycle (K18-D22) [A1'3, Nle8, K18, D22, L27 ] hPTH (1-31) NH2 (SEQ ID NO: 6) cycle (K18- 22 \ [rAA pl'.D6, NMlie? 0ß, K, 1l80, D2 ^ 2, | L 2 18 ' D ^) ^ 7-] hPTH (1-31) NH2 (SEQ ID NO: 9) cycle (KIB- D22) [A1'10, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 12) cycle (K18-D22) [A1'11, Nle8, K18, D22, L27] hPTH ( 1-31) NH2 (SEQ ID NO: 13) cycle (K18-D22) [A1'12, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 14) cycle (K18- D22) ) [A1'13, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 15) cycle (K18-D22) [A1'14, Nle8, K18, D22, L27] hPTH (1 -31) NH2 (SEQ ID NO: 16) cycle (K18-D22) [A1 5, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 17) cycle (K18-D22) [ A1'16, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 18) cycle (K18-D22) [A1'17, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 19) Cycle (K18-D22) [G1, Nie8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 20) Cycle (K18-D22) [A, G2 , Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 21) cycle (K18-D22) [A1, G3, Nle8, K18, D22, L27] hPTH (1-31) NH2 ( SEQ ID NO: 22) cycle (K18-D22) [A1, G10, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 29) cycle (K18-D22) [A1, G13, Nle8, K 8, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 31) cycle (K18-D22) [A1, G16, Nie8, K18, D22, L27] hPTH (1-31) NH2 ( SEQ ID NO: 34) cycle (K18-D22) [A1, G17, Nle8, K18, D 22, L27] hPTH (1-31) NH2 (SEQ ID NO: 35) cycle (K18-D22) [D- P1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 36 ) cycle (D18-D22) [A, Nle8, D18, K22, L27] hPTH (1-31) NH2 (SEQ ID NO: 47) cycle (018-D22) [A, Nle8.018, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 48) cycle (D18-022) [A1, Nle8, D18.022, L27] hPTH (1-31) NH2 (SEQ ID NO: 49) cycle (K18- E22) [A1, Nle8, K18, E22, L27] hPTH (1-31) NH2 (SEQ ID NO: 50) cyclo (O18-E22) [A1, Nle8, O18, E22, L27] hPTH (1-31) NH2 (SEQ ID NO: 51) cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-30) NH2 (SEQ ID NO: 52) cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-29) NH2 (SEQ ID NO: 53) cicio (K18- D22) [A1, Nle8, K18, D22, L27] hPTH (1-28) NH2 (SEQ ID NO: 54) cycle (K10-D14) [A1, Nle8'18, K10, D, L27] hPTH (1- 31) NH2 (SEQ ID NO: 66) cycle (K14-D18) [A1, Nle8, K14, D18, L27] hPTH (1-31) NH2 (SEQ ID NO: 67) cycle (K17-D21) [A1, Nle8'18, K17, D21, L27] hPTH (1-31) NH2 (SEQ ID NO: 68) cycle (K21-D25) [A1, Nle8 18, K21, D25, L27] hPTH (1-31) NH2 ( SEQ ID NO: 69) cycle (K25-D29) [A1, Nle8.18, K25, D29, L27] hPTH (1-31) NH2 (SEQ ID NO: 70) cycle (K18-D22) [K18, D22] hPTHrP (1-34) NH2 (SEQ ID NO: 71); cycle (K18-D22) [K18'26'30, D22, L23'28'31, E25'29] hPTHrP (1-34) NH2 (SEQ ID NO: 72) bicido (K13-D17, K18-D22) [ A1, Nle8, D17'22, K18, L27] hPTH (1-31) NH2 (SEQ ID NO: 73); bicyclo (K18-D22, K26-D30) [A1, Nle8, K8, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 74); tricycle (K13-D17, K18-D22, K26-D30) [A1, Nle8, K18, D17'22, L27] hPTH (1-31) NH2 (SEQ ID NO: 80); or a pharmaceutically acceptable salt or prodrug thereof. 21. A peptide compound according to claim 1, further characterized in that it is selected from: Cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 3) ) cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-34) NH2 (SEQ ID NO: 46) cycle (K18-D22) [A1'10, Nle8, K18, D22, L27 ] hPTH (1-31) NH2 (SEQ ID NO: 12) cycle (K18-D22) [A1'12, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 14) cycle ( K18-D22) [A1'13, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 15) cycle (K18-D22) [A1'14, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 16) cycle (K18-D22) [A1'16, Nle8, K8, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 18) cycle ( K18- (SEQ ID NO: 19) cycle (K 18 D22) [A1, G3, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 22) cycle (K18-D22) [A1, G13, Nle8, K18, D22, L27] hPTH ( 1-31) NH2 (SEQ ID NO: 31) cycle (K18-D22) [A1, G16, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 34) cycle (K18- D22) ) [A1, G17, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 35) cicio (K18-D22) [D-P1, Nle8, K18, D22, L27] hPTH (1 -31) NH2 (SEQ ID NO: 36) cycle (D18-D22) [A1, Nle8, D18, K22, L27] hPTH (1-31) NH2 (SEQ ID NO: 47) cycle (K18-E22) [A1 , Nle8, K 8, E22, L27] hPTH (1-31) NH2 (SEQ ID NO: 50) cycle (018-E22) [A, Nle8.018, E22, L27] hPTH (1-31) NH2 (SEQ ID NO: 51) Cycle (K18-D22) [A, Nle8, K18, D22, L27] hPTH (1 -30) NH2 (SEQ ID NO: 52) Cycle (K14-D18) [A1, Nle8, K14, D18 , L27] hPTH (1-31) NH2 (SEQ ID NO: 67) cycle (K18-D22) [K18, D22] hPTHrP (1-34) NH2 (SEQ ID NO: 71) bicyclo (K13-D17, K18- D22) [A1, Nle8, D17 22, K18, L27] hPTH (1-31) NH2 (SEQ ID NO: 73); bicyclo (K18-D22, K26-D30) [A, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 74); tricycle (K13-D17, K18-D22, K26-D30) [A1, Nle8, K18, D17'22, L27] hPTH (1-31) NH2 (SEQ ID NO: 80); or a pharmaceutically acceptable salt or prodrug thereof. 22. Bicycles (K13-D17, K26-D30) [A1, Nle8.18, D17, L27] hPTH (1-31) NH2 (SEQ ID NO: 79), or a pharmaceutically acceptable salt or prodrug thereof. 23. A peptide compound according to claim 4, or a pharmaceutically acceptable sai or prodrug thereof, further characterized in that X is selected from the group consisting of: (a) (b) R a-A5-A6-A7-A8-A9-; (c) R a-A6-A7-Ag-Ag-; (d) Ria-A7-A8-A9-; (e) R1a-A8-A9-; (f) R1b-Ag-; and (g) R1b-. 24. A peptide compound according to claim 23, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A8 is Nie and A27 is Leu. 25. A peptide compound according to claim 24, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that the side chains of Aβ8 and A22 are linked by means of an amide ligature to form a bridge. 26. A peptide compound according to claim 25, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that A? 0 is Asn or Asp; A13 is Lys; Au is His or Ser; A? 7 is Asp or Ser; A? 8 is Asp, Lys or Orn; A2? is Arg or Val; A22 is Asp, Glu, Lys or Orn; A25 is Arg or His; A26 is His or Lys; A2g is Ala or Gln and A30 is Asp or Glu. 27. A peptide according to claim 1, further characterized in that it is selected from: cycle (K18-D22) [K18, D22, L27] hPTH (10-31) NH2 (SEQ ID NO: 56) cycle (K18- D22) [K18, D22, L27] hPTH (9-31) NH2 (SEQ ID NO: 57); cycle (K18- 8? x18 rv22 i 27- 18 D ^) [NleB, K1B, D ^, L ^] hPTH (8-31) NH2 (SEQ ID NO: 58); cycle (KIB- ) NH2 (SEQ ID NO: 59); acid (K 18 D ^) [NleB, K1B, D L ^] hPTH (6-31) NH2 (SEQ ID NO: 60); cycle (K 18 _22. 8, x18 rv22, 27 18 D ^) [NleB, Kl0, D ^, L ^] hPTH (5-31) NH2 (SEQ ID NO: 61); cycle (K10- , 8? X18 r.22 i 27- 18 D ^) [NleB, K1B, D L¿ /] hPTH (7-34) NH2 (SEQ ID NO: 65) and cycle (K? B- D22) [K18, D22] hPTH (1-34) NH2 (SEQ ID NO: 77); or a pharmaceutically acceptable salt or prodrug thereof. 28. A pharmaceutical composition, characterized in that it comprises a peptide compound of claim 1, or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier. 29. The use of the peptide compound of claim 1, or a pharmaceutically acceptable sai or prodrug thereof, for the manufacture of a medicament for treating diseases associated with the regulation of calcium in a patient, wherein said compound or said salt or prodrug thereof, pharmaceutically acceptable, is delivered by pulsatile subcutaneous or intrapulmonary administration. The use of the peptide compound of claim 5, or a pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for treating diseases associated with the regulation of calcium in a patient. 31. The use according to claim 30, wherein said diseases related to the regulation of calcium in the body are selected from: hypocalcemia; osteopenia, osteoporosis, hyperparathyroidism, hypoparathyroidism, osteopenia induced by glucocorticoids and by immunosuppressants; and bone fracture and refracture. 32. The use of the peptide compound of claim 5 or a pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for treating osteopenia or osteoporosis in a host mammal. The use of the peptide compound of claim 4, or a pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for treating osteopenia or osteoporosis in a host mammal; wherein said compound, or a pharmaceutically acceptable salt or prodrug thereof, is delivered by pulsatile, subcutaneous or intrapulmonary administration. The use of the peptide compound of claim 23, or a pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for treating diseases associated with the regulation of calcium in a patient. 35. The use according to claim 34, wherein the diseases associated with the regulation of calcium in the body are selected from: hyper-hyperthyroidism and hypercalcemia crisis related to hyperparathyroidism; malignant hypercalcemia, renal failure and hypertension. 36. The use according to claim 34, wherein said compound or a pharmaceutically acceptable salt or prodrug thereof is delivered by subcutaneous or intrapulmonary pulsatile administration. 37.- A peptide compound of the formula: X-A? Q-Al 1 -Ai 2-A13-Au-Al 5-A16-A17-A18-A 9-A20-A2I -A22-A23-A24-A25-A26-A2 -Y or a pharmaceutically acceptable sai or prodrug thereof, wherein X is selected from the group consisting of: (a) Ria-Ao-A? -A2-A3-A4-As-A6-A7-A8-Ag-; (b) (c) R? b-A3-A4-A5-A6-A7-A8-A9-; (d) R1a- (e) R a-A5-A6-A7-A8-A9-; (f) R1a-A6-A7-A8-A9-; (g) A? a-A7-A8- Ag-; (h) Ria-As-Ag-; (i) R a-A9-; and (j) R? a; And it is selected from the group consisting of: (a) -R3, (b) -A28-R3, (c) -A28-A29-R3; (d) -A28-A29-A3o-R3; (e) -A28- A2g-A3o-A3? -R3; (f) -A28-A2g-A3o-A3i-A32-R3; (g) -A28-A29-A3o-A3i-A32-A33-R3; Y (h) -A28-A2g-A30-A3i-A32-A33-A34-R3; R1a is H, alkyl, aralkyl or -COR2; R1b is R? A or a group of the formula: R2 is alkyl, alkenyl, alkynyl, aryl or aralkyl; R3 is a group of the formula A35-OR4 or A35-NR4R5; R4 and R5 are independently H or lower alkyl; Rβ and Rg are independently H or alkyl; R7 is alkyl; R8 is H, alkyl or COR2; R10 is H or halogen; Rn is alkyl or aralkyl; Ao is absent or is a peptide of 1 to 6 amino acid residues; Ai is Ser, Ala, Gly or D-Pro, or an equivalent amino acid thereof; A2 is Ala, Val or Gly, or an equivalent amino acid thereof; A3 is Ala, Ser, Gly or D-Pro, or an equivalent amino acid thereof; is Glu, Ala or Gly or an amino acid equivalent to them; A5 is He, His, Ala or Gly or an equivalent amino acid thereof; A6 is Ala, Gln, Gly or D-Pro; or an equivalent amino acid of them; A is Ala, Leu or Gly, or an amino acid equivalent to them; A8 is Leu, Nie, Gly or D-Pro, or an amino acid equivalent to them; Ag is His, Ala, Gly or D-Pro, or an amino acid equivalent thereof; A 0 is Ala, Asn, Gly, Lys, Asp or D-Pro, or an amino acid equivalent to them; An is Ala, Gly, Leu or Lys, or an equivalent amino acid of them; A? 2 is Ala or Gly or an amino acid equivalent to them; A13 is Ala, Gly or Lys, or an amino acid equivalent to them; Au is Ala, Gly, His, Ser, Asp, Lys or D-Pro, or an amino acid equivalent to them; A 5 is Ala, Gly, He, D-Pro or Leu, or an amino acid equivalent to them; A? 6 is Asn, Ala, Gly, D-Pro or Gln, or an amino acid equivalent thereto; A? 7 is Ala, Asp, Gly, Ser, Lys or D-Pro, or an amino acid equivalent thereof; A? 8 is Lys or an equivalent amino acid thereof; A19 is Arg or Glu, or an amino acid equivalent to them; A2o is Arg, or an equivalent amino acid thereof; A2? is Arg, Lys, Asp or Val, or an equivalent amino acid thereof; A22 is Asp, Lys, Orn or Glu, or an equivalent amino acid thereof; A23 is Leu, Phe or Trp, or an amino acid equivalent to them; A24 is Leu or an equivalent amino acid thereof; A25 is Arg, His, Asp, Lys or Glu, or an amino acid equivalent thereof; A26 is Lys or His, or an amino acid equivalent to them; A2 is Leu or Lys, or an amino acid equivalent to them; A28 is He or Leu, or an amino acid equivalent to them; A2g is Ala, Asp, Glu or Gln, or an equivalent amino acid thereof; A30 is Asp, Lys or Glu, or an amino acid equivalent to them; A31 is lie, Leu or Val, or an amino acid equivalent to them; A32 is His or an equivalent amino acid thereof; A33 is Asn or Thr, or an amino acid equivalent to them; and A34 is Ala or Phe, or an equivalent amino acid thereof; and A35 is absent or is a peptide of 1 to 4 amino acids. 38. A peptide compound according to claim 37, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that R a is H and Y is NH 2. 39.- A peptide compound according to claim 38, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that X is: (a) A8-A9-; (b) R a-A2-A3-A_rA5-A6-A7-A8-Ag-; or (c) R a-A3-A4-A5-A6-A7-A8-Ag-. 40.- A peptide compound according to claim 39, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that Ai is Ser, Ala, Gly or D-Pro; A2 is Ala, Val or Gly; A3 is Ala, Ser. Gly or D-Pro; t is Glu, Ala or Gly; A5 is He, His, Aia or Gly; A6 is Ala, Gln, Gly or D-Pro; A7 is Ala, Leu, Gly; A8 is Leu, Nie, Gly or D-Pro; A9 is His, Ala, Gly or D-Pro; A10 is Ala, Asn, Gly, Asp O D-Pro; An is Ala, Gly, Leu O Lys; A? 2 is Ala or Gly; A13 is Ala, Gly or Lys; Au is Ala, Gly, His, Ser or D-Pro; A15 is Ala, Gly, He or D-Pro; A? 6 is Asn, Ala, Gly, D-Pro or Gln; A17 is Ala, Asp, Gly, Ser or D-Pro; A? 8 is Lys; A19 is Arg or Glu; A2o is Arg; A2? is Arg or Val; A22 is Asp, Lys, Orn or Glu; A23 is Leu, Phe or Trp; A24 is Leu; A25 is Arg or His; A26 is Lys or His; A27 is Leu or Lys; A28 is He or Leu, or an amino acid equivalent to them; A2g is Ala or Gln; A30 is Asp or Glu; A31 is He, Leu or Val; A32 is His; A33 is Asn or Thr; and A34 is Ala or Phe. 41.- A peptide compound according to claim 40, or a pharmaceutically acceptable salt or prodrug thereof acceptable, further characterized because Ai is Ala, Gly or D-Pro; A8 is Nie, A22 is Asp and A27 is Leu. 42. A peptide compound according to claim 41, or a pharmaceutically acceptable salt or prodrug thereof, further characterized in that X is R? AA? -A2-A3-A4-A5-A6-A7-A8-A9 -. 43.- A peptide compound according to claim 1, further characterized in that it is [A1, Nle8, K18D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 4) or a sai or a prodrug thereof, pharmaceutically acceptable 44. A pharmaceutical composition, characterized in that it comprises a peptide compound of claim 37 or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier. The use of the peptide compound of claim 37, or a pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for treating diseases associated with the regulation of calcium in a patient. 46. The use according to claim 45, wherein the diseases associated with the regulation of calcium in the body are selected from hypocalcemia, osteopenia, osteoporosis, hyperparathyroidism, hypoparathyroidism, glucocorticoid-induced osteopenia, and Immunosuppressants, and bone fracture and refracture. 47. The use of the peptide compound according to claim 37, or a pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for treating osteopenia or osteoporosis in a host mammal. 48. The use of the peptide compound of claim 38, or a pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for treating diseases associated with the regulation of calcium in a patient; wherein said pharmaceutically acceptable compound or said salt or said pharmaceutically acceptable prodrug thereof is delivered by subcutaneous or intrapulmonary pulsatile administration. 49.- A peptide compound according to claim 1, further characterized in that it is Cyclo (K18-D 2) [A1, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 3) or a pharmaceutically acceptable salt or prodrug thereof. 50.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-34) NH2 (SEQ ID NO: 46) or a salt or a prodrug thereof, pharmaceutically acceptable. 51.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1'10, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 12) or a pharmaceutically acceptable salt or drug thereof. 52. - A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1'12, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 14) or a salt or a prodrug thereof, pharmaceutically acceptable. 53.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1'13, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 15) or a pharmaceutically acceptable salt or prodrug thereof. 54.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1'14, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 16) or a pharmaceutically acceptable salt or prodrug thereof. 55.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1'16, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 18) or a pharmaceutically acceptable salt or prodrug thereof. 56.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A117, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 19) or a pharmaceutically acceptable salt or prodrug thereof. 57.- A peptide compound according to claim 1, further characterized in that it is cycle (K18- D22) [A1, G3, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 22) or a pharmaceutically acceptable salt or prodrug thereof. 58.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1, G13, Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 31) or a pharmaceutically acceptable salt or prodrug thereof. 59.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1, G16, Nle8, K18.D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 34) or a pharmaceutically acceptable salt or prodrug thereof. 60.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1, G17, Nle8, K8, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 35) ) or a pharmaceutically acceptable salt or prodrug thereof. 61.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [D- P \ Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 36) or a pharmaceutically acceptable salt or prodrug thereof. 62.- A peptide compound according to claim 1, further characterized in that it is cycle (D18-D22) [A1, Nle8, D18, K22, L27] hPTH (1-31) NH2 (SEQ ID NO: 47) or a salt or a prodrug thereof, pharmaceutically acceptable. 63. - A peptide compound according to claim 1, further characterized in that it is cyclo (K18-E22) [A1, Nle8, K18IE22) L27] hPTH (1-31) NH2 (SEQ ID NO: 50) or a salt or a prodrug of it, pharmaceutically acceptable. 64.- A peptide compound according to claim 1, further characterized in that it is cycle (018-E22) [A1, Nle8.018, E22, L27] hPTH (1-31) NH2 (SEQ ID NO: 51) or a salt or a prodrug thereof, pharmaceutically acceptable. 65.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [A1, Nle8, K18, D22, L27] hPTH (1-30) NH2 (SEQ ID NO: 52) or a salt or a prodrug thereof, pharmaceutically acceptable. 66.- A peptide compound according to claim 1, further characterized in that it is cycle (K14-D18) [A1, Nle8, K14, D18, L27] hPTH (1-31) NH2 (SEQ ID NO: 67) or a salt or a prodrug thereof, pharmaceutically acceptable. 67.- A peptide compound according to claim 1, further characterized in that it is cycle (K18-D22) [K18, D22] hPTHrP (1-34) NH2 (SEQ ID NO: 71) or a salt or a prodrug thereof , pharmaceutically acceptable. 68.- A peptide compound according to claim 1, further characterized because it is bicyclo (K13-D17, K18- D22) [A1, Nle8, D17'22, K18, L27] hPTH (1-31) NH2 (SEQ ID NO: 73) or a pharmaceutically acceptable salt or prodrug thereof. 69.- A peptide compound according to claim 1, further characterized in that it is bicyclo (K18-D22, K26-D30) [A \ Nle8, K18, D22, L27] hPTH (1-31) NH2 (SEQ ID NO: 74) or a pharmaceutically acceptable salt or prodrug thereof. 70.- A peptide compound according to claim 1, further characterized in that it is tricyclo (K13-D17, K18-D22, K26-D30) [A1, Nle8, K18, D17'22, L27] hPTH (1-31) NH2 (SEQ ID NO: 80) or a pharmaceutically acceptable salt or prodrug thereof.