NOVEL GROWTH HORMONE-RELEASING PEPTIDES AND METHOD OF TREATING MAMMALS THEREWITH

Abstract: The present invention relates to novel growth hormone-­ releasing peptides and method for increasing the release of growth hormone levels in mammals. The novel peptides of this invention surprisingly are effective for releasing growth hormone levels in animals by replacing the natural amino acids in positions 1, 2 and 3, as well as derivatizing the N-terminal amino acid residue in human pancreatic islet tumor origin growth hormone-releasing factor.

Description: NOVEL GROWTH HORMONE-RELEASING PEPTIDES AND METHOD OF TREATING MAMMALS THEREWITH BACKGROUND OF THE INVENTION The present invention relates to novel growth hormone-releasing peptides and method for increasing the release of growth hormone levels in mammals therewith. Recently, growth hormone-releasing factors (GRF) of human pancreatic islet tumor origin (hpGRF) were isolated, characterized, and shown to possess growth hormone(GH)-releasing activity in rat anterior pituitary in vitro and in vivo by (1) R. Guillemin, P. Brazeau, P. Böhlen, F. Esch, N. Ling, and W. B. Wehrenberg [Science, 218, 585 (1982)1 and (2) J. Spiess, J. Rivier, M. Thorner. and W. Vale [Biochemistry, 21, 6037 (1982)j. Further. a synthetic hp GRF(1-29)-NH2, an amidated fragment of the natural hp GRF, was reported to possess fu)l intrinsic biological activity by Spiess et al. (,f reverence (2). AMINO ACID SEQUENCE IN DESIGNATED PEPTIDES hpGRF (1-44)NH2 (Guillemin) Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg 1 Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Aly-Ala 29 40 Arg-Ala-Arg-Leu-NH2; 44 hpGRF (1-40) (Vale) Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg 1 Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala; 29 40 hpGRF (1-29)NH2 Tyr-Ala-Asp-Ala-Ile-Phe-The-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg 1 Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2. 29 Code for L-Amino Acid, per IUPAC-IUB Commission on Biochemical Nomenclature: Biochemistry 11, 1726-1732 (1972) His = Histifine Val = Valine Tyr = Tyrosine Gln = Glutamine Ser = Serine Phe = Phenylalanine Arg = Arginine Met = Methionine Asp = Aspartic Acid Thr = Threonine Leu - Leucine Ile = Isoleucine Ala = Alanine Asn = Asparagine Lys = Lysine Glu = Glutamic Acid Gly = Glycine Since these hpGRF peptides contain 29 to 44 amino acid units with their molecular weights ranging from 3,085 to 5,035 Daltons, it is desirable to increase their potency so that the dosages administered for practical purpose could be reduced for eliciting the release of suitable levels of GH in mammals. It is, therefore, an object of the present invention to provide more potent peptides which mimic hpGRF and are effective for increasing the release of growth hormone to suitable levels in mammals. SUMMARY OF THE INVENTION Surprisingly, this objective is achieved by replacing the natural amino acids in positions 1, 2, and 3, as well as derivatizing the N-terminal amino acid residue in hpGRF 1 to 29, 1 to 40 and 1 to 44 as expressed below by the structural formulas (I), (II), and (III) respectively. These results are unexpected, especially in view of reports by N. Ling and P. Brazeau [The Endocrine Society Program and Abstracts, 65th Annual Meeting, No. 295, June 8 to 1Q, 1983it at San Antonio, Texas] which indicate that Ac-Tyrl and D Tyrl hpGRF analogs have low potency with respect to the natural peptide, and by J. Rivier et al. [Abstract 8th American Peptide Symposium, May 22-27, 1983, paper 10-B], who indicated for hpGRF (1-27) "some manipulation of the Tyr residue is compatible as long as a free amino terminus is conserved." DESCRIPTION OF THE INVENTION The polypeptides of the present invention are depicted by the structures of formulas (I), (II), and (III) below: : R1-A-B-C-Ala-Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu 1 10 Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y 20 Ser-Arg-R2 29 (I) RÚ-A-B-C-Ala-Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu 1 Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Glu-Asp-Ile-Y Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-R2 29 40 (II) RÚ-A-B-C-Ala-Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-val-Leu 1 Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Alat 29 Arg-Ala-Arg-Leu-R2 44 (III) Wherein R1 is hydrogen or C1-C6 straight- or branched-chain alkanoyl; R2 is NR3R4 or OR3, wherein R3 and R4 are selected from the group consisting of hydrogen and a straight- or branched-chain alkyl group containing 1-6 carbon atoms; A represents a member selected from tyrosyl, D-tyrosyl, histidyl, D-histidyl, phenylalanyl, D-phenylalanyl, 4-chlorophenylalanyl, D-4-chlorophenylalanyl, 4-bromophenylalanyl, D-4-bromoalanyl, 4-fluorophenylalanyl, D-4-fluorophenylalanyl, 4-methoxyphenylalanyl, D-4-methoxyphenylalanyl, 4-benzyloxyphenylalanyl, D-4-benzyl oxyphenylalanyl, tryptophyl, D-tryptophyl, 5-fluorotryptophyl, D-5-fluorotryptophyl, 5-chlorotryptophyl, D-5-chlorotryptophyl, 5-bromotryptophyl, D-5-bromotryptophyl, 5-methoxytryptophyl, D-5-methoxytryptophyl, 5-methyltryptophyl, D-5-methyltryptophyl or EMI7.1 B represents a member selected from alanyl, D-alanyl, leucyl, D-leucyl, phenylalanyl, D-phenylalanyl, 4chlorophenylalanyl, D-4-chlorophenylalanyl, 4-bromophenylalanyl, D-4-bromophenylalanyl, 4-fluorophenylalanyl, D-4-fluorophenylalanyl, 4-methoxyphenylalanyl, D-4-methoxyphenylalanyl, 4-benzyloxyphenylalanyl, D-4benzyloxyphenylalanyl, tryptophyl, D-tryptophyl, 5fluorotryptophyl, D-5-fluorotryptophyl, 5-chlorotryptophyl, D-5-chlorotryptophyl, 5-bromotryptophyl, D-5-bromotryptophyl, 5-methoxytryptophyl, D-5-methoxytryptophyl or EMI7.2 C represents a member selected from aspartyl, D-aspartyl, D-aspartyl, glutamyl and D-glutamyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the proviso that when R1 is hydrogen and B is alanyl and C is aspartyl, and X is asparaginyl, and Y is methionyl, A cannot be tyrosyl in Formula (I), (II) or (III); and when R1 is hydrogen or alkanoyl and B is alanyl and C is aspartyl, and.X is asparaginyl, and Y is methionyl, A cannot be phenylalanyl, tryptophyl, histidyl, or D-tyrosyl in Formula (II) or (III); and the pharmaceutically acceptable salts thereof. Preferred compounds of the invention are represented by Formulas (I), (II), or (III) wherein R1, R2, R3, and R4 are selected from those described above; and A is selected from tyrosyl, D--tyrosyl, histidyl, D-histidyl; B is selected from alanyl, D-alanyl, leucyl, D-leucyl; C is selected from aspartyl, D-aspartyl, glutamyl and D-glutamyl; X is selected from asparaginyl or D-asparaginyl; Y is selected from norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. Another preferred group of compounds of the invention have the Formula (I) configuration, wherein R1 is selected from hydrogen or Cl-C3 alkanoyl; R2 is NR3R4 or OR3; R3 and R4 are each selected from hydrogen and C1-C3 alkyl; A is selected from tyrosyl, Dtyrosyl or histidyl; B is alanyl or 1)-alanyl; C ïs aspartyl or D-aspartyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. The most preferred group of compounds of the invention have the Formula (I) configuration, wherein R1 is selected from hydrogen or acetyl. R2 is NH2; A is selected from tyrosyl, D-tyrosyl or histidyl; B is alanyl or D-alanyl; C is aspartyl or D-aspartyl; X is asparaginyl or D-asparaginyl; and Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. The term "pharmaceutically acceptable salts" as used herein refers to non-toxic alkali metal, alkaline earth metal, ammonium, organoammonium and metallic salts commonly used in the pharmaceutical industry. These salts include, but are not limited to, the sodium, potassium, lithium, calcium, magnesium, zinc, ammonium, and trimethylammonium salts which are prepared by methods well known in the art. The term also includes non-toxic acid addition salts such as hydro chloride, hydrobromide, acetate, phosphate, sulfate, citrate, laurate, stearate, pamoate, and oleate, but are not limited to them. These acid addition salts are also prepared by methods well known in the art. In keeping with the standard nomenclature, abbreviations for chiral amino acid residues used in the present specification and claims are as follows: Abbreviation Name His L-histidyl Ser L-serinyl Asp L-aspartyl D-Asp D-aspar tyl Ala L-alanyl D-Ala D-alanyl Val L-valinyl Phe L-phenylalanyl Thr L-threonyl Asn L- aspar aginyl D-Asn D-asparaginyl Tyr L-tyrosinyl Arg L-arginyl Leu L-leucyl D-Leu D-leucyl Nle L-norleucyl Lys L-lysyl Gln L-glutaminyl Met L-methionyl Ile L-isoleucyl Glu L-glutamyl D-Glu D-glutamyl D-Tyr D-tyrosyl D-His D-histidyl D-Phe D-phenylalanyl (4-Cl)Phe L-4-chlorophenylalanyl D- (4-Cl)Phe D-4-chlorophenylalanyl (4-Br)Phe L-4-bromophenylalanyl Abbreviation Name D-(4-Br)Phe D-4-bromophenylalanyl (4-F)Phe L-4-fluorophenylalanyl D-(4-F)Phe D-4-fluorophenylalanyl (4-MeO)Phe L-4-methoxyphenylalanyl D-(4-MeO)Ph3 D-4-methoxyphenylalanyl (4-CH20)Phe L-4-benzloxyphenylalanyl D-(4-CH20)Phe D-4-benzloxyphenylalanyl Trp L- tryptophyl D-Trp D- tryptophyl (5-F)Trp L-5-fluorotryptophyl D-(5-F)Trp D-5-fluorotryptophyl (5-Cl)Trp L-5-chlorotryptophyl D-(5-Cl)Trp D-5-chlorotryptophyl (5-Br)trp L-5-bromotryptophyl D-(5-Br)Trp D-5-bromotryptophyl (5-MeO)Trp L-5-methoxytryptophyl D-(5-MeO)Trp D-5-methoxytryptophyl (5-Me)Trp L-5-methyltryptophyl D-(5-Me)Trp D-5-metbyltryptophyl Unless otherwise specified, the amino acid residues that are named herein without the prefix L will refer to the naturally occurring absolute configuration L. The R1 group refers to the substituent on the N-terminus amino acid (position 1) of the peptide according to standard nomenclature. Other abbreviations used in the present specification are: Fmoc = fluorenylmethyloxycarbonyl Boc = t-butyloxycarbonyl Tos E-toluenesulfonyl hplc = high-performance liquid chromatography tlc = thin-layer chromatography TFA = trifluoroacetic acid Ac = acetyl Solid-phase synthesis of the Formulas (I), (II), and (III) peptides can be carried out on a Beckman 990 automatic peptide synthesizer. Preparative HPLC can be performed on a thick-walled glass column (2.5 x 45 cm) containing Whatman LRP-1 reverse phase packing (C18 silica 13-20 um) pumped with Fluid Metering Company pump and pulse damper. Amino acid analyses can be run on a Beckman 119 CL analyzer and processed with a System AA computing integrator. Amino acid derivatives utilized in the preparation of the compounds of the present invention are available from several chemical supply houses including: Bachem, Inc., Torrance, California, and Chemical Dynamics, Inc., Plainfield, New Jersey. The peptides having the Formulas (I), (If), and (III) configurations can be conveniently prepared by standard solid-phase techniques; for example, the C-terminal protected amino acid can be attached to a chloromethyl resin, a hydroxymethyl resin, a benzhydrylamine (BHA) resin, or a p-methylbenzylhydrylamine (2-Me-BHA) resin. One such chloromethyl resin is sold under the trade name Bio-Beads SX-l by Bio Rad Laboratories, Richmond, California. The preparation of the hydroxymethyl resin is described by Bodansky et al., Chem. Ind. (London) 38, 1597 (1966). The BHA resin has been described by Pietta andtashall, Chem, Commun. 650 (1970) and commercially available from Bachem, Inc., Torrance, California. According to an embodiment of the invention, the peptides of Formulas (I), (II), and (III) are prepared by means of solid-phase peptide synthesis by standard procedures, although it may also be prepared by treatment of the peptide-resin with ammonia to give the desired side-chain protected amide or with an alkylamine to give a side-chain protected alkylamide or dialkylamide. The a-amino protecting group is Fmoc, and the side-chain protecting group is t-Bu instead of benzyl for the appropriate amino acid when the chloromethyl or hydroxymethyl resin is used. Side-chain protection can then be removed in the usual fashion by treatment with HF to give the free peptide amides, alkylamides, or dialkylamides. In preparing the esters of this invention, the resins used to prepare the acids of Formulas (I), (11), and (III) (R2 = OH) can be employed, and the side-chain protected peptide can be cleaved with a base and an appropriate alcohol, i.e., methanol. Side-chain protecting groups can then be removed in the usual fashion by treatment with HF to obtain the desired ester. The solid-phase procedure discussed above is well known in the art and has been essentially described by Stewart and Young, Solid Phase Peptide Synthesis, Freeman and Company, San Francisco, California (1969). - FLOW DIAGRAM I Preparation of [D-Alaê]-hpGRF(1-29)-NH2 EMI13.1 <tb> BHA <SEP> Resin <SEP> + <SEP> Boc-Arg(Tos) <tb> <SEP> (CH3) <SEP> 2CH-N-C=N-CH(CH3) <SEP> 2 <tb> <SEP> \ <SEP> FH2C12 <SEP> JA <tb> <SEP> Boc-Arg(Tos)-BHA <SEP> Resin <tb> <SEP> (a) <SEP> CH2C12 <SEP> wash <tb> <SEP> (b) <SEP> 33% <SEP> TFA/CH2C12, <SEP> twic <tb> <SEP> (c) <SEP> CH2C12 <SEP> wash <SEP> ice <tb> <SEP> (d) <SEP> EtOH <SEP> wash <tb> <SEP> (e) <SEP> CH2C12 <SEP> wash <tb> <SEP> (f) <SEP> Et3N/CHC13, <SEP> twice <tb> <SEP> (g) <SEP> CH2C12 <SEP> wash <tb> <SEP> V <tb> <SEP> Boc-Arg(Tos)-BHA <SEP> Resin <tb> <SEP> (1) <SEP> Boc-Ser(CH2), <SEP> A, <SEP> B <tb> <SEP> (2) <SEP> Boc-Met, <SEP> A, <SEP> B <tb> <SEP> (3) <SEP> Boc-Ile, <SEP> A, <SEP> B <tb> <SEP> (4) <SEP> Boc-Asp(CH2), <SEP> A, <SEP> B <tb> <SEP> (5) <SEP> Boc-Gln, <SEP> A, <SEP> B <tb> <SEP> (6) <SEP> Boc-Leu, <SEP> A, <SEP> B <tb> <SEP> (7) <SEP> Boc-Leu, <SEP> A, <SEP> B <tb> <SEP> (8) <SEP> Boc-Lys(4-ClCH20CO), <SEP> A, <SEP> B <tb> <SEP> (9) <SEP> Boc-Arg(Tos), <SEP> A, <SEP> B <tb> <SEP> (10) <SEP> Boc-Ala, <SEP> A, <SEP> B <tb> <SEP> (11). <SEP> Boc-Ser(CH2), <SEP> A, <SEP> B <tb> <SEP> (12) <SEP> Boc-Leu, <SEP> A, <SEP> B <tb> <SEP> (13) <SEP> Boc-Gln, <SEP> A, <SEP> B <tb> <SEP> (14) <SEP> Boc-Gly, <SEP> A, <SEP> B <tb> <SEP> (15) <SEP> Boc-Leu, <SEP> A, <SEP> B <tb> <SEP> (16) <SEP> Boc-Val, <SEP> A, <SEP> B <tb> <SEP> (17) <SEP> Boc-Lys(4-C1BCH20CO), <SEP> A, <SEP> B <tb> <SEP> (18) <SEP> Boc-Arg(Tos), <SEP> A, <SEP> B <tb> <SEP> 519) <SEP> Boc-Tyr(4-BrCH20co) <SEP> A, <SEP> B <tb> FLOW DIAGRAM I (Continued) EMI14.1 <tb> <SEP> (20) <SEP> Boc-Ser(CH2), <SEP> A, <SEP> B, <tb> <SEP> MeOH <SEP> wash, <SEP> cycle <SEP> B <tb> <SEP> (21) <SEP> Boc-Asn, <SEP> A, <SEP> B <tb> <SEP> (22) <SEP> .Boc-Thr(BCH2), <SEP> A, <SEP> B <tb> <SEP> (23) <SEP> Boc-Phe, <SEP> A, <SEP> B <tb> <SEP> (24) <SEP> Boc-Ile, <SEP> A, <SEP> B <tb> <SEP> (25) <SEP> Boc-Ala, <SEP> A, <SEP> B <tb> <SEP> (26) <SEP> Boc-AspCCH2), <SEP> A, <SEP> B <tb> <SEP> (27) <SEP> Boc-D-Ala, <SEP> A, <SEP> B <tb> <SEP> (28) <SEP> Boc-Tyr, <SEP> A, <SEP> B <tb> <SEP> V <tb> D-Ala2hpGRF(1-29)-BHA <SEP> Resin <tb> <SEP> (a) <SEP> HF, <SEP> dimethylsulfide, <tb> <SEP> p-cresol <tb> <SEP> (b) <SEP> Et20 <SEP> wash <tb> <SEP> (c) <SEP> HOAc, <SEP> Sephadex <SEP> G-50 <SEP> column <tb> <SEP> chromatography <tb> <SEP> (d) <SEP> Lyophilize <tb> <SEP> (e) <SEP> Chromatography: :octadecyl <tb> <SEP> silane <SEP> silica, <SEP> 15-50% <tb> <SEP> CH3CN/H20/0.1% <SEP> TFA/80 <SEP> psi <tb> <SEP> (f) <SEP> Lyophilize <tb> <SEP> V <tb> <SEP> [D-Ala2]-hpGRF(1-29)-NH2 <tb> To prepare formula (II) analogs, the C-terminal protected amino acid Boc-alanine is attached to the desired resin as described for preparing formula (I) peptides; likewise, to prepare formula (III) analogs, the C-terminal protected amino acid Boc-leucine is attached to the desired resin. The subsequent amino acid groups are then sequentially coupled to the solid phase in the manner described in Flow Diagram I. To prepare a N-terminal alkanoyl [R1 of (I), (II), and (III)] peptide, the peptide bonded to the resin is allowed to stir in 5 to 20% solutions of the appropriate acid anhydride in CH2C12 containing tri ethyl amine or other standard acid accepting bases for 20 to 120 minutes at room temperature. Subsequently, the standard reagents for cleaving the peptide from the resin is used to obtain the desired peptide of formulas (I), (II), or (III). Thus, by the above-mentioned procedure, the following peptides are prepared: [N-Acetyl]-hpGRF(1-29)-NH2 D-Tyrl]-hpGRF(1-29)-NH2 [N-Acetyl-D-Tyrl]-hpGRF(1-29)-NH2 [N-Acetyl,D-Ala2]-hpGRF(1-29)-NH2 [D-Asp3] -hpGRFCl-29) -NH2 [N-Acetyl ,D-Asp3 ] -hpGRF(1-29)-NH2 [D-Tyrl ,D-Ala2]-hpGRF(1-29) -NH2 [N-Acetyl-D-Tyrl,D-Ala2]-hpGRF(1-29)-NH2 [HisÚ,D-Alaê]-hpGRF(1-29)-NH2 [N-Acetyl-HisÚ,D-Alaê]-hpGRF(1-29)-NH2 [D-TyrÚ,D-Alaê,D-Asp ]-hpGRF(1-29)-NH2 [N-Acetyl-D-TyrÚ,D-Alaê,D-Asp ]-hpGRF(1-29)-NH2 [HisÚ,D-Alaê,D-Asp ]-hpGRF(1-29)-NH2 [N-Acetyl-HisÚ,D-Alaê,D-Asp ]-hpGRF(1-29)-NH2 [PheÚ]-hpGRF(1-29)-NH2 [N-Acetyl-Phel]-hpGRF(1-29)-NH2 [D-Asn8]-hpGRF(1-29)-NH2 [D-Alaê,Nle27]-hpGRF(1-29)-NH2 [Hisl,D-Ala2,Nle27]-hpGRF(1-29)-NH2 [D-Alaê,D-Asn8,Nle27]-hpGRF(1-29)-NH2 [D-Asp3,D-Asn8,Nle27]-hpGRF(1-29)-NH2 [D-Alaê,D-Asp ,D-Asn8,Nle27]-hpGRF(1-29)-NH2 [D-Phel]-hpGRF(1-29)-NH2 [N-Acetyl-D-PheÚ]-hpGRF(1-29)-NH2 [D-Hisl ]-hpGRF(1-29)-NH2 [N-Acetyl-D-HisÚ]-hpGRF(1-29)-NH2 [D-Leu2]-hpGRF(1-29)-NH2 [N-Acetyl,D-Leu2]-hpGRF(1-29)-NH2 [D-Phe2]-hpGRF(1-29)-NH2 [N-Acetyl,D-Phe2]-hpGRF(1-29)-NH2 [Asp ]-hpGRF(1-29)-NH2 [N-Acetyl,Asp3]-hpGRF(1-29)-NH2 [D-Glu3]-hpGRF(1-29)-NH2 [N-Acetyl,D-Glu3]-hpGRF(1-29)-NH2 [D-Alaê]-hpGRF(1-40)-NH2 [D-Ala2 ] -hpGRFCl-44) -NH2 [N-Acetyl,D-Ala2]-hpGRF(1-40)-NH2 [N-Acetyl,D-Ala2]-hpGRF(1-44)-NH2 Accordingly, the present invention includes pharmaceutical compositions comprising at least one of the peptides of formulas (I), (II), or (III) as an active ingredient, in association with a pharmaceutical carrier or diluent for use in stimulating growthhormone release in mammals as follows: R1-A-B-C-Ala-Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y-5er- Arg-R2; (I) or R1-A-B-C-Ala- Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu- Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y-Ser Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Gl u-Arg-Gly-Ala-R2 (II) or R1-A-B-C-Ala-I le-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu- Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y-Ser Arg-Gln-Gln-Gly-Glu-Ser-Asn-Glu-Glu-Arg-Gly-Ala-Arg Ala-Arg-Leu-R2; (III) wherein R1 is hydrogen or C1-C6 straight- or branchedchain alkanoyl; R2 is NR3R4 or OR3; R3 and R4 are selected from the group consisting of hydrogen and a straight- or branched-chain alkyl group containing one to six carbon atoms; A represents a member selected from tyrosyl, D-tyrosyl, histidyl, D-histidyl, phenylalanyl, D-phenylalanyl, 4-chlorophenylalanyl, D-4chlorophenylalanyl, 4-bromophenylalanyl, D-4-bromoalanyl, 4-fluorophenylalanyl, D-4-fluorophenylalanyl, 4-methoxyphenylalanyl, D-4-methoxyphenylalanyl, 4benzyloxyphenylalanyl, D-4-benzyloxyphenylalanyl, tryptophyl, D-tryptophyl, 5-fluorotryptophyl, D-5fluorotryptophyl, 5-chlorotryptophyl, D-5-chlorotryptophyl, 5-bromotryptophyl, D-5-bromotryptophyl, 5-methoxytryptophyl, D-5-methoxytryptophyl, 5-methyltryptophyl, D-5-methyltryptophyl or EMI17.1 B represents a member selected from alanyl, D-alanyl, leucyl, D-leucyl, phenylalanyl, D-phenylalanyl, 4chlorophenylalanyl, D-4-chlorophenylalanyl, 4-bromophenylalanyl, D-4-bromophenylalanyl, 4-fluorophenylalanyl, D-4-fluorophenylalanyl, 4-methoxyphenylalanyl, D-4-methoxyphenylalanyl, 4-benzyloxyphenylalanyl, D-4benzyloxyphenylalanyl, tryptophyl, D-tryptophyl, 5fluorotryptophyl, D-5-fluorotryptophyl, 5-chlorotryptophyl, D-5-chlorotryptophyl, 5-bromotryptophyl, D-5-bromotryptophyl, 5-methoxytryptophyl, D-5-methoxytryptophyl or EMI18.1 C represents a member selected from aspartyl, D-aspartyl, glutamyl and D-glutamyl; X represents asparaginyl or D-asparaginyl; Y represents norleucyl or methionyl; with the proviso that when R1 is hydrogen, B is alanyl, C is aspartyl, X is asparaginyl and Y is methionyl, A cannot be tyrosyl in Formulas (I), (II), and (III) or phenylalanyl, tryptophyl, histidyl or D-tyrosyl in Formulas (II) and (III); and the pharmaceutically acceptable salts thereof. In practice, it has been found that the Formulas (I), (II), and CIII) compounds of the present invention are effective for increasing the release of growth hormone in mammals when administered thereto in an amount sufficient to provide said-treated mammals with from 0.000001 to 0.1 mg/kg of mammalian body weight/day of said Formulas (I), (II), or (III) compound. Preferred peptides for increasing release of growth hormone in mammals have a structure selected from Formulas (I), (II), or (III) above, wherein R1, R2, R3, and R4 are selected from those described above; A is tyrosyl, D-tyrosyl, histidyl, D-histidyl; B is alanyl, D-alanyl, leucyl, D-leucyl; C is aspartyl, D-aspartyl, glutamyl, or D-glutamyl; X is asparaginyl or D-asparginyl; Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. Another preferred group of compounds of the present invention effective for increasing growth hormone-release in mammals have the structure illustrated by Formula (I) wherein R1 is hydrogen or C1-C3 alkanoyl; R2 is NR3R4 or OR3; R3 and R4 are each hydrogen or a straight- or branched-chain or C1-C3 alkyl; A is tyrosyl, D-tyrosyl, or histidyl; B is alanyl or D-alanyl; C is aspartyl or D-aspartyl; X is asparaginyl or D-asparginyl; Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. The most preferred group of compounds of the invention have the Formula (I) configuration, wherein R1 is selected from hydrogen or acetyl; R2 is NH2; A is selected from tyrosyl, D-tyrosyl or histidyl; B is alanyl or D-alanyl; C is aspartyl or D-aspartyl; X is asparaginyl or D-asparaginyl; and Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. These peptides are useful for treatment of symptoms related to growth hormone deficiencies, for increasing wool growth, for increasing rate of growth of meat-producing animals, for improving carcass quality in meat-producing animals (i.e., more protein and less fat), for improving feed efficiency in meat-producing animals and dairy cows, for increasing milk production in dairy herds, and in healing wounds. In order to facilitate a further understanding of the invention, the following examples are presented primarily for the purpose of illustrating certain more specific details thereof. The invention is not to be deemed limited thereby except as defined in the claims. EXAMPLE 1 Protected human pancreatic growth bormone-releasing factor(9-29)-benzhydrylamine resin Benzhydrylamine polystyrene resin (commercially available from Bachem, Inc., Torrance, California) (6.0 g, 3.00 mmol) in the chloride ion form is placed in the reaction vessel of a Beckman 990 automatic peptide synthesizer programmed to carry out the following work-wash cycle: (a) CH2C12; (b) 33% trifluoroacetic acid in CH2C12 (two times for one and 25 minutes each); (c) CH2C12; (d) C2H5OH; (e) CH2C12; (f) 10% (C2H5)3N in CHCl3 (two times for two minutes each); and (g) CH2C12. The neutralized resin is stirred with t-butyloxycarbonyl(Boc)-N-tosyl-l-arginine [Boc-Arg(Tos)] and diisopropylcarbodiimide (6 mmol) in CH2C12 for one hour, and the resulting amino acid resin is then cycled through the steps (a) through (g) in the above wash program. The following L-amino acids (3 mmol) are then coupled successively by the same reaction cycle: Boc-Ser(benzyl), Boc-Met, Boc-Ile, Boc- Asp(benzyl), Boc-Gln, Boc-Leu, Boc-Leu, Boc-Lys(4chlorocarbenzoxy), Boc-Arg(Tos), Boc-Ala, Boc Ser(benzyl), Boc-Leu, Boc-Gln, Boc-Gly, Boc-Leu, Boc Val, Boc-Lys(4-chlorocarbenzoxy), Boc-Arg(tosyl), Boc Tyr(4-bromocarbenzoxy) and Boc-Ser(benzyl), except that Boc-Gln was coupled in the presence of l-hydroxybenzotriazole (6 mmol) in dimethylformamide solution. The completed peptide-benzhydrylamine resin, with the N-terminal Boc group removed, was then washed with CH30H and air dried to give 11.79 g of material. EXAMPLE 2 Preparation of protected D-tyrosine-l-human pancreaticgrowth hormone-releasinz factorfl-29)-benzhydrYlamine resin Peptide benzhydrylamine resin (0.98 g, 0.25 mmol) containing the 9-29 residues of the peptide as described in Example 1 is subjected to the work-wash cycle also described in Example 1. The neutralized resin is stirred with Boc-L-asparagine (0.75 mmol), diisopropylcarbodiimide (0.75 mmol), and l-hydroxy- benzotriazole (0.75 mmol) in dimethylformamide. The following amino acid derivatives (0.75 mmol) are then coupled successively by the same treatment cycle described in Example 1: Boc-Thr(benzyl), Boc Phe, Boc-Ile, Boc-Ala, Boc-Asp(benzyl), Boc-Ala, and Boc-D-Tyr. The completed 1-29 peptide resin is then cycled through the standard work-wash program described in Example 1 in order to remove the N-terminal Boc group. EXAMPLE 3 Preparation of D-tyrosine-l-human pancreatic growth hormone-releasing(l-29)-amide [(D-Tyrl)-hpGRF(1-29)-NH2] A mixture of the 1-29 peptide resin described in Example 2 (0.75 mmol) and a solution of hydrogen fluoride (10 mL), dimethylsulfide (26 mL), and p-cresol (4 mL) are stirred at 0 C for 75 minutes. Excess reagents are then rapidly evaporated under a stream of dry nitrogen and hydrogen fluoride (35 mL) is added, and the mixture stirred for a further 45 minutes at 0 C. Excess hydrogen fluoride is evaporated under nitrogen, and the resin plus free peptide are washed free of g-cresol with a large volume of diethyl ether. The peptide is extracted into 50% acetic acid solution and applied to a column (2.5 x 95 cm) of Sephadex G-50 which is eluted with 2 M acetic acid. Eluant is monitored at 280 nM and fractions containing a major uv-absorbing peak are pooled and lyophilized. A solution of the lyophilized powder is eluted on a column (1.5 x 45 cm) of octadecylsilane silica having a mesh size of 15-20 M and pore size of 300 Ao (purchased from Vydac, Hesperia, California). A linear elution gradient of 15-50% acetonitrile in 0.1% trifluoroacetic acid solution was employed at a pumping pressure of about 80 psi. Emerging fractions are monitored at 280 nm and are each examined by analytical hplc at a wave length of 215 nm in order to ensure maximum homogeneity of pooled fractions. Lyophilization of these gave the title peptide as a white powder (32 mg). This material gave one peak emerging at 38.minutes using analytical hplc on a column (0.4 x 25 cm) of Vydac octadecylsilane silica (5 M mesh size, 300 Ao) which is pumped at 2 mL/min with a linear gradient of 20 to 40% acetonitrile in 0.1% trifluoracetic acid. Tlc on silica gel using the solvent system l-butanol: pyridine: acetic acid: water (15:10:3:12) gave one spot as visualized by chlorine-starch spray reagent. Amino acid analysis of a 6 M HC1 hydrolysate gave the following amino acid ratios: Asp, 3.08; Thr, 1.08; Ser, 3.01; Glu, 2.22; Gly, 1.10; Ala, 3.30; Val, 0.87; Met, 0.97; Ile, 1.69; Leu, 3.61; Tyr, 1.60; Phe, 1.05; Lys, 2.07; Arg, 3.28. EXAMPLE 4 Preparation of protected N- a' cetyl human pancreatic growth hormone-releasing factor(l-29)-benzhydrylamine resin Peptide-benzhydrylamine resin(9-29) (0.98 g, 0.25 mmol) prepared in Example 1 was subjected to the coupling cycles described in Example 2, except that L-Tyr was used in place of D-Tyr. The 1-29 peptide resin, with the N-terminal Boc group removed, was acetylated by stirring with a 10% solution of acetic anydride/Et3N in methylene chloride (30 minutes). EXAMPLE 5 Preparation of N-acetyl human pancreatic growth hormone-releasing factor(l-29)-amide (N-acetyl-hpGRF(l29)-NH2) The peptide resin (0.75 mmol) described in Example 4 was treated with hydrogen fluoride mixtures and purified as described in Example 3. The lyophilized, purified peptide weighed 16.2 mg. This material gave one peak emerging at 36.5 minutes using the analytical hpic conditions described in Example 3. Tic using the conditions also described in Example 3 gave one spot. Amino acid analysis of a 6 M HC1 hydrolysate gave the following amino acid ratios: Asp, 3.05; Thr, 1.08; Ser, 2.96; Glu, 2.20; Gly, 1.20; Ala, 3.30; Val, 0.81; Met, 1.00; Ile, 1.65; Leu, 3.50; Tyr, 1.61; Phe, 1.20; Lys, 2.10; Arg, 3.17. EXAMPLE 6 Preparation of protected D-alanine2-human pancreatic growth hormone-releasing factor(1-29)-benzhydrylamine resin Peptide-benzhydrylamine resin (0.98 g, 0.25 mmol) prepared in Example 1 was subjected to the coupling cycles described in Example 2, except that Dalanine was used in place of L-alanine in position 2 and L-tyrosine in place of D-tyrosine in position 1. EXAMPLE 7 Preparation of D-alanineê-human pancreatic growth hormone-releasing(1-29)-amide [(D-Alaê)-hpGRF(1-29)-NH2] The peptide resin (0.25 mmol) described in Example 6 is treated with hydrogen fluoride mixtures and purified as described in Example 3. The purified, lyophilized peptide weighed 27.9 mg. This material gave one peak emerging at 35 minutes using the analytical hplc conditions as described in Example 3. Tlc using the conditions described in Example 3 gave one spot. Amino acid analysis of a 6 M HC1 hydrolysate gave the following amino. acid ratios: Asp, 3.06; Thr, 1.07; Ser, 3.05; Glu, 2.19; Gly, 1.02; Ala, 3.29; Val, 0.94; Met, 1.10; Ile, 1.72; Leu, 3.66; Tyr, 1.62; Phe, 0.90; Lys, 2.07; Arg, 3.19. EXAMPLE 8 Preparation of protected D-aspartic acid3-human pancreatic growth hormone-releasing factor(l-29)benzhydrylamine resin Peptide-benzhydrylamine resin (0.98 g, 0.25 mmol) prepared in Example 1 was subjected to the coupling cycles described in Example 2, except that D-aspartic acid was used in place of L-aspartic acid in position 3 and L-tyrosine in place of D-tyrosine in position 1. EXAMPLE 9 Preparation of D-aspartic acid3-human pancreatic growth hormone-releasing(l-29)-amide [(D-Asp3)-hpGRF(1-29)-NH2] The peptide resin (0.25 mmol) described in Example 8. is treated with hydrogen fluoride mixtures and purified as described in Example 3. The purified, lyophilized peptide weighed 15.3 mg. This material gave one peak emerging at 34 minutes using the analytical hplc conditions as described in Example 3. Tlc using the conditions described in Example 3 gave one spot. Amino acid analysis of a 6 M HC1 hydrolysate gave the following amino acid ratios: Asp, 3.17; Thr, 1.22; Ser, 3.08; Glu, 2.36; Gly, 1.06; Ala, 3.30; Val, 0.96; Met, 0.84; Ile, 1.76; Leu, 3.71; Tyr, 1.00; Phe, 0.92; Lys, 2.21; Arg, 3.30. EXAMPLE 10 Preparation of protected N-acetyl-D-tyrosinel,D- alanine'-human pancreatic growth hormone-releasing factor(l-29)-benzhydrylamine resin Peptide-benzhydrylamine resin (0.98 g, 0.25 mmol) prepared in Example 1 was subjected to the coupling cycles described in Example 2, except that D-alanine was used in place of L-alanine in position 2 and D-tyrosine in place of L-tyrosine in position 1. EXAMPLE 11 Preparation of N-acetyl-D-tyrosinel,D-alanine2-human pancreatic growth hormone-releasing(1-29)-amine [(N acetyl-D-Tyrl,D-Ala2)-hpGRF(1-29)-NH2] The peptide resin (0.25 mmol) described in Example 10 is treated with hydrogen fluoride mixtures and purified as described in Example 3. The purified, lyophilized peptide weighed 5 mg. This material gave one peak emerging at 33 minutes using the analytical hpic conditions as described in Example 3. TIc using the conditions described in Example 3 gave one spot. Amino acid analysis of a 6 M HC1 hydrolysate gave the following amino acid ratios: Asp, 3.08; Thr, 1.08; Ser, 3.01; Glu, 2.22; Gly, 1.10; Ala, 3.30; Val, 0.87; Met, 0.97; Ile, 1.69; Leu, 3.61; Tyr, 1.60; Phe, 1.05; Lys, 2.07; Arg, 3.28. EXAMPLE 12 Preparation of protected N-acetyl-D-tyrosinel,Dalanineê,D-aspartic acid -human pancreatic growth hormone-releasing factor(1-29)-benzhydrylamine resin Peptide-benzhydrylamine resin (0.98 g, 0.25 mmol) prepared in Example 1 was subjected to the coupling cycles described in Example 4, except that D-aspartic acid was used in place of L-aspartic acid in position 3, D-alanine in place of L-aspartic acid in position 2, and D-tryosine in place of L-tyrosine in position 1. EXAMPLE 13 Preparation of N-acetyl-D-tyrosinel,D-alanine2,D- aspartic acid > -human pancreatic growth hormonereleasing(l-29)-amide [(N-acetyl-DTyr1,D-Ala2,D Asp3) -hpGRF (1-29)-NH2] The peptide resin (0.25 mmol) described in Example 12 is treated with hydrogen fluoride mixtures and purified as described in Example 3. The purified, lyophilized peptide weighed 12 mg. This material gave one peak emerging at 34 minutes using the analytical hplc conditions as described in Example 3. Tic using the conditions described in Example 3 gave one spot. Amino acid analysis of a 6 M HC1 hydrolysate gave the following amino acid ratios: Asp, 3.06; Thr, 1.07; Ser, 3.00; Glu, 2.18; Gly, 1.11; Ala, 3.30; Val, 0.82; Met, 0.97; Ile, 1.62; Leu, 3.43; Tyr, 1.69; Phe, 0.92; Lys, 2.03; Arg, 3.13. EXAMPLE 14 Preparation of protected N-acetyl-tosyl-L-histidine1,D-alanine-2-human pancreatic growth hormonereleasing factor(l-29)-benzhydrylamine resin Peptide-benzhydrylamine resin (0.98 g, 0.25 mmol) prepared in Example 1 was subjected to the coupling cycles described in Example 4, except that D-alanine in place of L-alanine in position 2, and L-tosyl-histidine in place of L-tyrosine in position 1. EXAMPLE 15 Preparation of N-acetyl-L-histidine-1,D-alanine2- human pancreatic growth hormone-releasing(l-29)-amine [(N-acetyl-HisÚ,D-Alaê)-hpGRF(1-29)-NH2] The peptide resin (0.25 mmol) described in Example 12 is treated with hydrogen fluoride mixtures and purified as described in Example 3. The purified, lyophilized peptide weighed 18 mg. This material gave one peak emerging at 31 minutes using the analytical hplc conditions as described in Example 3. Tic using the conditions described in Example 3 gave one spot. Amino acid analysis of a 6 M HC1 hydrolysate gave the following amino acid ratios: Asp,.3.06; Thr, 1.01; Ser, 3.00; Glu, 2.26; Gly, 1.10; Ala, 3.30; Val, 0.79; Met, 0.97; Ile, 1.69; Leu, 3.71; Tyr, 0.81; Phe, 0.96; His, 0.95; Lys, 2.15; Arg, 3.30. EXAMPLE 16 The following N-acyl (R1) growth hormone-releasing factors(l-29) of structural Formula (I) are prepared by using the methods described in Example 4 and Example 5 by substituting the following acid anhydrides for acetic anhydride and the appropriate GRF(1-29), wherein R2 is NH2. Anhydr ide R1 GRF(1-29) HCO-O-COCH3 HCO hp (CH3CH2CO) 20 CH3CH2CO hp [(CH3)2CH-CO]20 (CH3)2CHCO hp [CH3(CH2)4CO]2) CH3(CH2)4CO hp [(CH3)3CCO]20 (CH3)3CCO lD-Ala2]-hp 1 (CH3)2CH-CO]20 (CH3)2CHCO [D-Ala2]-hp (CH3(CH2)3C0)20 CH3(CH2)3CO [D-Ala2)-hp (CH3CO)2O CH3CO [D-Alaê]-hp [CH3(CH2)4C0]20 CH3(CH2)4C0 [D-Ala2]-hp HCO-O-COCH3 HCO [D-Ala2]-hp CH3(CH2)2CO CH3(CH2)CO [D-Alaê]-hp (CH3CO)20 CH3CO [D-Asp3]-hp [CH3(CH2)4CO]2CO CH3(CH2)4CO [D-Asp ]-hp (CH3CH2CO)2O CH3CH2CO [HisÚ,D-Alaê]-hp [(CH3)2CHCO]2O (CH3)2CHCO [HisÚ,D-Alaê]-hp CH3(CH2)4CO CH3(CH2)4CO [HisÚ,D-Alaê]-hp HCO-OCOCH3 HCO <RTI ID=28.6> [D-Tyr1,D-Ala2]-hp (CH3CH2CO)2O CH3CH2CO [D-TyrÚ,D-Alaê]-hp [(CH3)2CHCO]2O (CH3)2CHCO [D-TyrÚ,D-Alaê]-hp [CH3(CH2)3CO]2O CH3(CH2)3CO [D-TyrÚ,D-Alaê]-hp [CH3(CH2)4C0]20 CH3(CH2)4CO [D-Tyr1,D-Ala2]-hp [(CH3)3CCO]2O (CH3)2CCO [D-TyrÚ,D-Alaê]-hp HCOOCH3 HCO [D-TyrÚ,D-Alaê,D-Asp ]-hp (CH3CH2CO)2O CH3CH3CO [D-TyrÚ,D-Alaê,D-Asp ]-hp [(CH3)2CHCO]2O (CH3)2CHCO [D-TyrÚ,D-Alaê,D-Asp ]-hp [CH3(CH2)3CO]2O CH3(CH2)3CO [D-TyrÚ,D-Alaê,D-Asp ]-hp [(CH3)3CCO]2O (CH3)3CCO [D-TyrÚ,D-Alaê,D-Asp ]-hp The superscripts used in this Example, which are assigned to given amino acid residues, indicate the locations of said residues in the amino acid sequence of the synthesized growth hormone-releasing peptides. EXAMPLE 17 Evaluation of peptide effects on growth hormone release in mammals using the rat as the test species In this evaluation, the procedures described by W. A. Murphy et al., Endocrinology 109:491-495 (1980), were employed. In growth hormone (GH) experiments, male rats (Charles Rivers) were anesthetized with NEMBUTAL (6 mg per 100 g body weight) which also served to maintain stimulated plasma GH levels. Exactly 30 minutes after the rats were anesthetized, 0.5 mL of saline or the test peptide in saline was administered as a SC bolus. A 1 mL blood sample was drawn from the jugular vein 15 minutes after the injection of the peptide in saline. GH levels were determined using NIADDKD rat GH RIA components. hpGRF(1-29)-NH2 Structure-Activity Studies Dose Plasma GH Analog ( g/100 g BW) (ng/mL) Saline - 333 # 50 (5)* [N-Ac-D-TyrÚ,D-Alaê] hpGRF(1-29)-NH2 0.05 499 t 50 (5) [N-Ac-D-TyrÚ,D-Alaê] hpGRF(1-29)-WH2 0.2 680 + 100 (7) [N-Ac-D-TyrÚ,D-Alaê] hpGRF(1-29)-NH2 0.8 2063 # 251 (6) [N-Ac-D-TyrÚ,D-Alaê] hpGRF(1-29)-NH2 3.2 3818 t 412 (6) * Number of rats in parenthesis GRF(1-29)-NH2 Dose Plasma GH* Analog ( g/100g BW) (ng/ml) Saline - 366 + 81 (6) (a) D-Asn8 4 1296 # 118 (5) " 10 2397 # 246 (6) Saline - 278 + 37 (6) (b) D-Alaê-Nle27 0.1 465 # 75 (6) " 1.0 2287 # 265 (6) Saline - 214 + 29 (6) (c) HisÚ-D-Alaê-Nle27 0.1 094 # 111 (6) " 1.0 3379 # 389 (6) Saline - 203 + 39 (8) (d) D-Alaê-D-Asn8-Nle27 0.05 407 # 53 (6) " 0.5 1613 # 138 (6) Saline - 383 + 79 (6) (e) D-Asp3-D-Asn8-N1e27 0.1 810 + 86 (6) 1.0 3213 + 590 (6) (f) D-Alaê-D-Asp -D-Asn8-Nle27 0.1 767 # 146 (6) " 1.0 2419 # 252 (6) Potencies were determined by comparison to pooled standards: GRF(1-29)-NH2 10 1185 + 74 (78) " 25 2570 + 121 (70) *Values are the mean + SEM (n). EXAMPLE 18 Preparation of D-asparagine8-human pancreatic growth hormone-releasing(1-29)-amide [(D-Asn8)-hpGRF(1-29)-NH2] The peptide-benzhydrylamine resin (0.25 mmoles of resin) prepared in Example 1 was subjected to the coupling cycles described in Example 2, except that D-asparagine was used in place of L-asparagine in position 8. The yield was 38 mg, and the peptide had HPLC elution time of 28 minutes at a flow rate of 1.5 mL/minutes. The amino acid analysis gave: Asp, 3.05; Thr, 0.95; Ser, 2.96; Glu, 2.21; Gly, 1.04; Ala, 3.02; Val, 0.95; Ile, 1.85; Leu, 2.00; Nle 0.97; Tyr, 2.10; Phe, 0.96; Lys, 1.97; Arg, 3.20. EXAMPLE 19 Preparation of D-alanine2, norleucine27-human pancreatic growth hormone-releasingtl-29)-amide [(D-Ala2, N1e27)-hpGRFCl-29)-NH2] The peptide-benzhydrylamine resin was prepared as in Example 1 with L-norleucine replacing L-methionine in position 27 of the coupling cycle. A Boc protecting group on L-norleucine was used. This material was then coupled in the manner described in Example 2 with D-alanine relacing L-alanine in position 2. The yield was 71 mg from 0.25 mmole of resin used, and the HPLC elution time was 28.5 minutes with a flow rate of 1.5 mL/minutes. The amino acid anal ysis gave: Asp, 3.06; Thr, 1.00; Ser, 2.96; Glu, 2.20; Gly, 1.06; Ala, 3.10; Val, 0.90; Ile, 1.78; Leu, 4.08; Nle, 1.00; Tyr, 1.96; Phe, 0.88; Lys, 2.00; Arg, 3.14. EXAMPLE 20 Preparation of histidinel, D-alanine2, norleucine27human pancreatic growth hormone-releasing(1-29)-amide [ (Hisl ,D-Ala2,Nle27)-hpGRF(l-29)-NH2] The peptide-benhydrylamine resin was prepared as in Example 1 with L-norleucine replacing L-methionine in position 27 of the coupling cycle. This material was then coupled in the manner described in Example 2 with L-histidine replacing L-tyrosine in position 1 and D-alanine replacing L-alanine in position 2. The yield was 23 mg from 0.25 mmole of resin used, and the HPLC elution time was 27.5 minutes at a flow rate of 1.5 mL/minutes. The amino acid analysis gave: Asp, 3.13; Thr, 1.00; Ser, 2.98; Glu, 2.27; Gly, 1.10; Ala, 3.15; Val, 0.99; Ile, 1.88; Leu, 4.20; Nle, 1.05; Tyr, 0.98; Phe, 0.91; His, 1.17; Lys, 2.01; Arg, 3.11. EXAMPLE 21 Preparation of D-alanine2, D-asparagine8, norleucine27human pancreatic growth hormone-releasing(l-29)amide [CD-Ala2, D-Asn8, Nle27)-hpGRF(1-29)-NH2] The peptide-benzhydryl resin was prepared as in Example 1 with L-norleucine replacing L-methionine in position 27 of the coupling cycle. This material was then coupled in the manner described in Example 2 with D-alanine replacing L-alanine in position 2 and Dasparagine replacing L-asparagine in position 8. The yield was 41 mg from 0.25 mmole of resin used, and the HPLC elution time was 28.5 minutes at a flow rate of 1.5 mL/minutes. The amino acid analysis gave: Asp, 2.99; Thr, 1.00; Ser, 2.87; Glu, 2.14; Gly, 1.06; Ala, 3.04; Val, 0.93; Ile, 1.80; Leu, 4.02; Nle, 0.98; Tyr, 1.99; Phe, 0.90; Lys, 2.01; Arg, 3.08. EXAMPLE 22 Preparation of D-aspartic acid3, D-asparagine8, noreucine=/-human pancreatic growth hormone releasing(l-29)-amide [(D-Asp3, D-Asn8, Nle27)-hpGRF(1-29)-NH2] The peptide-benzhydtyl resin was prepared as in Example 1 with L-norleucine replacing L-methionine in position 27 of the coupling cycle. This material was then coupled in the manner described in Example 2 with D-aspartic acid replacing L-aspartic acid in position 3 and D-asparagine replacing L-asparagine in position 8. The yield was 114 mg starting with 0.25 mmole of resin, and the HPLC elution time was 29.1 minutes at a flow rate of 1.5 mL/minutes. The amino acid analysis gave: Asp, 2.99; Thr, 1.00; Ser, 2.85; Glu, 2.16; Gly, 1.03; Ala, 3.03; Val, 0.94; Ile, 1.82; Leu, 4.03; Nle, 0.99; Tyr, 1.97; Phe, 0.92; Lys, 2.06; Arg, 3.05. EXAMPLE 23 Preparation of D-alanineê, D-aspartic acid , D-asparagine8, norleucine27-human pancreatic growth hormone releasing(l-29)-amide [(D-Ala2, D-Asp3, D-Asn8, Nle27)- hpGRF(1-29)-NH2] The peptide-benzhydryl resin was prepared as in Example 1 with L-norleucine replacing L-methionine in position 27 of the coupling cycle. This material was then coupled in the manner described in Example 2 with D-alanine replacing L-alanine in position 2, D-aspartic acid replacing L-aspartic acid in position 3 and D-asparagine replacing L-asparagine in position 8. The yield was 67 mg starting with 0.25 mmole of resin, ad the HPLC elution time was 28 minutes at a flow rate of 1.5 mL/minutes. The amino acid analysis gave: Asp, 3.01; Thr, 1.00; Ser, 2.90; Glu, 2.20; Gly, 1.05; Ala, 3.08; Val, 0.95; Ile, 1.86; Leu, 4.01; Nle, 0.96; Tyr, 1.95; Phe, 0.93; Lys, 2.05; Arg, 3.11.

Claims: WHAT IS CLAIMED IS: 1. A peptide characterized by the formula: R1 A-B-C-Ala-Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu-Gly Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y-Ser-Arg R2; (I) or R1-A-B-C-Ala-I le-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val -Leu- Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y- Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala R2; (II) or R1-A-B-C-Ala-Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu- Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y-Ser Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg Ala-Arg-Leu-R2; (III) wherein R1 is hydrogen or C1-C6 straight- or branchedchain alkanoyl; R2 is NR3R4 or OR3; R3 and R4 are selected from the group consisting of hydrogen and a straight- or branched-chain alkyl group containing one to six carbon atoms; A is tyrosyl, D-tyrosyl, histidyl, D-histidyl; B is alanyl, D-alanyl, leucyl, Dleucyl; C is aspartyl, D-aspartyl, glutamyl and Dglutamyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the proviso that when R1 is hydrogen, and B is alanyl, and C is aspartyl, and X is asparaginyl, and Y is methionyl, A cannot be tyrosyl in Formulas (I), (II) or (III); and when R1 is hydrogen or alkanoyl, and B is alanyl, and C is aspartyl, and X is asparaginyl, and Y is methionyl, A cannot be phenylalanyl, tryptophyl, histidyl, or Dtyrosyl in Formulas (II) or (III); and the pharmaceutically acceptable salts thereof. 2. A peptide according to Claim 1, wherein is selected from hydrogen or C1-C3 alkanoyl; R2 is NR3R4 or OR3; R3 and R4 are each selected from hydrogen and C1-C3 alkyl; A is tyrosyl, D-tyrosyl, histidyl; B is alanyl or D-alanyl; C is aspartyl or Daspartyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. 3. A peptide according to Claim 1, having the Formula (I) structure wherein R1 is selected from hydrogen or acetyl; R2 is NH2; A is tyrosyl, D-tyrosyl, or histidyl; B is alanyl or D-alanyl; C is aspartyl or D-aspartyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. 4. The peptide according to Claim 1 characterized by the formula: Tyr-D-Ala-Asp-Ala-Ile-Phe Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-Ala-D-Asp-Ala I le-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu- Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; D-Tyr-Ala Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser Arg-NH2 and its pharmaceutically acceptable salts; Ac Tyr-Ala-Asp-Aia-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val- Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Ac-His-D-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Ac-D-Tyr-D-Asp-Ala-Ile-Phe-Thr-Asn Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Ac-D-Tyr-D-Ala-Asp-Ala Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-Ala Asp-Ala-Ile-Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly- Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser- Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala-Asp-Ala-I le-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val- Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; His-D-Ala-Asp-Ala-Ile-Phe-Thr-D-Asn-Ser-Tyr Arg-T.ys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu- Gln-Asp-Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-D-Asn Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys Leu-Leu-Gln-Asp-Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-Ala-D-Asp-Ala-Ile Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala-D Asp-Ala-Ile-Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly- Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Nle-Ser Arg-NH2 and its pharmaceutically acceptable salts; or Ac-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys- Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts. 5. A method for increasing the release of growth hormone in mammals, said method characterized by administering thereto from 0.000001 to 0.1 mg/kg of mammalian body weight/day of a peptide having the formula: Rl-A-B-c-Ala-Ile-phe-Thr-x-ser-Tyr-Arg-Lys-val-Le Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y Ser-Arg-R2; (I) or RÚ-A-B-C-Ala-Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-IleY-Ser- Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-R2; (II) or R1-A-B-C-Ala-I le-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu- Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-I le-Y-Ser- Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg Ala-Arg-Leu-R2; (III) wherein R1 is hydrogen or C1-C6 straight- or branchedchain alkanoyl; R2 is NR3R4 or OR3; R3 and R4 are selected from the group consisting of hydrogen and a straight- or branched-chain alkyl group containing one to six carbon atoms; A is tyrosyl, D-tyrosyl, histidyl, D-bistidyl; B is alanyl, D-alanyl, leucyl, Dleucyl; C is aspartyl, D-aspartyl, glutamyl and Dglutamyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the proviso that when R1 is hydrogen, B is alanyl, and C is aspartyl, and X is asparaginyl and Y is methionyl; A cannot be tyrosyl in Formulas (I), (II), and (III) or phenylalanyl, tryptophyl, histidyl or D-tyrosyl in Formulas (II) and (III); and the pharmaceutically acceptable salts thereof. 6. A method according to Claim 5, wherein R1 is selected from hydrogen or C1-C3 alkanoyl; R2 is NR3R4 or OR3; R3 and R4 are each selected from hydrogen and C1-C3 alkyl; A is tyrosyl7 D-tyrosyl or histidyl; B is alanyl or D-alanyl; C is aspartyl or D-aspartyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. 7. A method according to Claim 5, wherein the peptide is of the Formula (I); R1 is hydrogen or acetyl; R2 is NH2; A is tyrosyl, D-tyrosyl, or histidyl; B is alanyl or D-alanyl; C is aspartyl or D-aspartyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the above-mentioned proviso; and the pharmaceutically acceptable salts thereof. 8. A method according to Claim 5, wherein the peptide is [D-A1a2]-hpGRF(1-29)-NH2; Tyr-Ala-Asp-Ala Ile-Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Nle-Ser Arg-NH2 and its pharmaceutically acceptable salts; His-D-Ala-Asp-Ala-Ile-Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-D-Asn-Ser Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu Leu-Gln-Asp-Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-Ala-D-Asp-Ala-Ile-Phe Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala Arg-Lys-Leu-Leu-Gln-Asp-Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala-D-Asp Ala-Ile-Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Nle-Ser-Arg- NH2 and its pharmaceutically acceptable salts; or Ac Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val- Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts. 9. A process for the preparation of a peptide having the formula, R1-A-B-C-Ala-Ile-Phe-Thr-X-Ser Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu Leu-Gln-Asp-lle-Y-Ser-Arg-R2; (I) or Rl-A-B-C-Ala-Ile-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y-Ser- Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-R2; (II) or Rl-A-B-C-Ala-lle-Phe-Thr-X-Ser-Tyr-Arg-Lys-Val-Leu- Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Y-Ser Arg-Gln-Gln-Gly-Flu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg Ala-Arg-Leu-R2; (III) wherein R1 is hydrogen or C1-C6 straight- or branchedchain alkanoyl; R2 is NR3R4 or OR3; R3 and R4 are selected from the group consisting of hydrogen and a straight- or branched-chain alkyl group containing one to six carbon atoms; A is tyrosyl, D-tyrosyl, histidyl, D-histidyl; B is alanyl, D-alanyl, leucyl, Dleucyl; C is aspartyl, D-aspartyl, glutamyl and Dglutamyl; X is asparaginyl or D-asparaginyl; Y is norleucyl or methionyl; with the proviso that when R1 is hydrogen, and B is alanyl, and C is aspartyl, and X is asparaginyl, and Y is methionyl, A cannot be tyrosyl in Formulas (I), (II) or (III); and when R1 is hydrogen or alkanoyl, and B is alanyl, and C is aspartyl, and X is asparaginyl, and Y is methionyl, A cannot be phenylalanyl, tryptophyl, histidyl, or Dtyrosyl in Formulas (II) or (III); and the pharmaceutically acceptable salts thereof; said method comprising: a C-terminal protected amino acid to a resin in the present of a coupling agent; washing with an inert solvent; deprotecting in the presence of an acid; repeating this sequence with the subsequent protected amino acids as defined in formula (I), (II) and (III), stepwise, from the C-terminus of the peptide; and finally detaching the peptide from the resin the presence of an acid to afford the peptide of formula (I), (II) and (III), wherein said resin is BRA or p-ME-BHA; or detaching the peptide from the resin with ammonia, alkylamine or dialkylamine and deprotecting with an acid to afford the peptide of formula (I), (II) and (III), wherein said resin is a chlormethylated or hydroxymethylated resin; or detaching the peptide from the resin in the presence of an acid to afford the peptide of the formula (I), (II) or (III), wherein said resin is a chloromethylated or hydroxymethylated resin; or detaching the peptide from the resin in the presence of a base and an R30H alcohol, followed by acid treatment to afford the peptide of the formula (I), (II) or (III), wherein R3 is a straight- or branched chain alkyl group containing one to six carbon atoms and said resin is a chloromethylated or hydroxymethylated resin. 10. A process for the preparation of a peptide according to Claim 9, wherein said peptide is characterized by the formula: Tyr-D-Ala-Asp-Ala-Ile-Phe- Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-Ala-D-Asp-Ala Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; D-Tyr-Ala Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser Arg-NH2 and its pharmaceutically acceptable salts; Ac Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Ac-His-D-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Ac-D-Tyr-D-Asp-Ala-Ile-Phe-Thr-Asn Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys- Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Ac-D-Tyr-D-Ala-Asp-Ala Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-Ala Asp-Ala-Ile-Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly- Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val- Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; His-D-Ala-Asp-Ala-Ile-Phe-Thr-D-Asn-Ser-Tyr- Arg-Lys-Val -Leu-Gly-Gln-Leu-Ser-Ala""Arg-Lys-Leu-Leu- Gln-Asp-Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-D-Asn- Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys Leu-Leu-Gln-Asp-Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; ; Tyr-Ala-D-Asp-Ala-Ile- Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Nle-Ser-Arg-NH2 and its pharmaceutically acceptable salts; Tyr-D-Ala-D Asp-Ala-Ile-Phe-Thr-D-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Nle-Ser Arg-NH2 and its pharmaceutically acceptable salts; or Ac-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys- Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp- Ile-Met-Ser-Arg-NH2 and its pharmaceutically acceptable salts.

Inventors: COY, DAVID HOWARD, MURPHY, WILLIAM ANDREW
Applicants: ADMINISTRATORS OF THE  TULANE EDUCATIONAL FUND
Application year: 1984
Main classification: C07K7
IPC codes: C07K14, A61P5, A61K38