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Details for Patent: 4,563,352

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Details for Patent: 4,563,352

Title: Human pancreatic GRF
Abstract:Human pancreatic GRF has been synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-R.sub.15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-S er-Asn-Gln-Glu-Arg-Gly-R.sub.40 -R.sub.41 -R.sub.42 -Y wherein R.sub.15 is Gly or D-Ala, R.sub.40 is Ala or des-R.sub.40, R.sub.41 is Phe or des-R.sub.41, R.sub.42 is des-R.sub.42 or 1 to 8 different amino acid residues selected from the group consisting of Gln, Gly, Ile, Leu, Lys, Pro, Thr and Val, and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical -COOR.sub.1,-CR.sub.1 O,-CONHNHR.sub.1,-CON(R.sub.1)(R.sub.2) or -CH.sub.2 OR.sub.1, with R.sub.1 and R.sub.2 being lower alkyl or hydrogen. These peptides or biologically active fragments thereof, or analogs thereof having well-known substitutions and/or additions, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to animals, including humans, and may be used diagnostically.
Inventor(s): Rivier; Jean E. F. (La Jolla, CA), Spiess; Joachim (Encinitas, CA), Vale, Jr.; Wylie W. (La Jolla, CA)
Assignee: The Salk Institute For Biological Studies (San Diego, CA)
Filing Date:Oct 04, 1982
Application Number:06/432,663
Claims:1. A synthetic peptide having the formula: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-D-Ala-Gln-Leu-Se r-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-G lu-Arg-Gly-R.sub.40 -Y wherein R.sub.40 is Ala or des-R.sub.40, and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical --COOH or --CONH.sub.2, or a fragment thereof extending from the N-terminus to a residue in position 28 through 39 which is biologically active to effect the release of GH from the pituitary, or a nontoxic salt thereof.

2. A synthetic peptide having the formula of claim 1 wherein Y is CONH.sub.2.

3. A synthetic peptide having the formula of claim 1 wherein Y is COOH.

4. A synthetic peptide having the formula of claim 2 wherein R.sub.40 is des-R.sub.40.

5. A synthetic peptide having the formula of claim 2 wherein R.sub.40 is Ala.

6. A pharmaceutical composition for stimulating the release of GH in an animal comprising an amount of the peptide of claim 1 or a nontoxic salt thereof effective to stimulate the release of GH from the pituitary, and a pharmaceutically acceptable liquid or solid carrier therefor.

7. A method of stimulating the release of growth hormone in an animal, which comprises administering to said animal an effective amount of a pharmaceutical composition as defined in claim 6.

8. A method in accordance with claim 7 wherein said administering is carried out either intravenously, subcutaneously, intramuscularly or intranasally.

9. A method of stimulating the release of GH in a mammal by administering an effective amount of a compound as defined in claim 2.

10. A method for accelerating the growth of nonhuman animals comprising administering an effective amount of a synthetic peptide defined by the formula: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-D-Ala-Gln-Glu-Se r-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-R.sub.30 -R.sub.31 -R.sub.32 -NH.sub.2 wherein R.sub.30 is Gln or des-R.sub.30, R.sub.31 is Gln or des-R.sub.31, R.sub.32 is Gly or des-R.sub.32, or a nontoxic salt thereof.

11. A method in accordance with claim 10 wherein R.sub.28 is Ser and R.sub.29 is Arg.

12. A method in accordance with claim 11 wherein R.sub.30 is des-R.sub.30, R.sub.31 is des-R.sub.31 and R.sub.32 is des-R.sub.32.

13. A method in accordance with claim 11 wherein R.sub.30 is Gln, R.sub.31 is Gln and R.sub.32 is Gly.
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