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Claims for Patent: 4,517,181

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Claims for Patent: 4,517,181

Title: Mammalian PGRF
Abstract:PGRF 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: ##STR1## wherein R is OH or NH.sub.2, R.sub.34 is Ser or Ala, R.sub.38 is Arg or Ser, R.sub.40 is Ala or Arg and R.sub.41 is Arg, Arg-Ala, Arg-Ala-Arg, Arg-Ala-Arg-Leu or des-R.sub.41. 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 mammals, including humans, and may be used diagnostically.
Inventor(s): Ling; Nicholas C. (San Diego, CA), Esch; Frederick S. (Oceanside, CA), Bohlen; Peter (Encinitas, CA), Brazeau, Jr.; Paul E. (San Diego, CA), Guillemin; Roger C. L. (La Jolla, CA)
Assignee: The Salk Institute for Biological Studies (San Diego, CA)
Application Number:06/418,248
Patent Claims: 1. A synthetic peptide having the formula: ##STR12## wherein R is OH or NH.sub.2, R.sub.34 is Ser or Ala, R.sub.38 is Arg or Ser, R.sub.40 is Ala or Arg and R.sub.41 is Arg, Arg-Ala, Arg-Ala-Arg or Arg-Ala-Arg-Leu, or a fragment of such peptide which fragment is biologically active to effect the release of GH, or a nontoxic salt of such peptide or peptide fragment.

2. A synthetic peptide having the formula of claim 1 wherein R.sub.34 is Ser, R.sub.38 is Arg and R.sub.40 is Ala.

3. A synthetic peptide having the formula of claim 2 wherein R.sub.41 is Arg-Ala-Arg-Leu.

4. A synthetic peptide having the formula of claim 3 wherein R is NH.sub.2.

5. A synthetic peptide having the formula of claim 3 wherein R is OH.

6. A method of stimulating the release of GH in mammals by administering an effective amount of a synthetic peptide as defined in claim 1.

7. A method of improving muscle mass in nonhuman animals by administering an amount of a compound as defined in claim 1 which is effective to accelerate anabolism.

8. A pharmaceutical composition comprising a synthetic peptide as defined in claim 1 in an amount effective to stimulate the release of GH in a human and a pharmaceutically acceptable liquid or solid carrier therefor.

9. A method of stimulating the release of growth hormone in an animal, which comprises administering an effective amount of a synthetic peptide having the sequence: ##STR13## or a fragment of such peptide which fragment is biologically active to effect the release of GH by the pituitary, or a nontoxic salt of such peptide or peptide fragment.

10. A method in accordance with claim 9 for stimulating the release of GH in nonhuman animals.

11. A method of improving growth in farm animals in accordance with claim 10 by administering an amount effective to accelerate anabolism.

12. A method in accordance with claim 9 wherein the carboxyl terminus is free acid or amide.

13. A method for stimulating the release of GH in a human in accordance with claim 10 by administering said effective amount in combination with a pharmaceutically acceptable liquid or solid carrier therefor.

14. A method in accordance with claim 1 wherein said synthetic peptide is a biologically active fragment of the 40-residue peptide including the N-terminal sequence thereof.

15. A method in accordance with claim 14 wherein the carboxyl terminus is free acid.

16. A method in accordance with claim 14 wherein the carboxyl terminus is amide.

17. A pharmaceutical composition comprising an effective amount of a synthetic peptide having the sequence: ##STR14## wherein and R.sub.41 is Arg, Arg-Ala, Arg-Ala-Arg or Arg-Ala-Arg-Leu, or a fragment of such peptide which fragment is biologically active to effect the release of GH by the pituitary, or a nontoxic salt of such peptide or peptide fragment, plus an acceptable nontoxic liquid or solid carrier therefor, said amount being effective to stimulate the release of GH.

18. A composition in accordance with claim 17 wherein R.sub.41 is Arg-Ala-Arg-Leu.

19. A composition in accordance with claim 18 wherein the carboxyl terminus is amide.

20. A composition in accordance with claim 18 wherein the carboxyl terminus is free acid.
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