| abstract |
Human pancreatic GRF(hpGRF), rat hypothalamic GRF(rGRF) and porcine hypothalamic GRF(pGRF) have been earlier characterized and synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans, which have resistance to enzymatic degradation in the body, and which contain the sequence: R 1 -R 2 -R 3 -Ala-Ile-Phe-Thr-R 8 -Ser-R 10 - Arg-R 12 -R 13 Leu-R 15 - Gln-R 17 -R 18 - Ala-Arg-Lys-Leu- R 23 -R 24 -R 25 - lle- R 27 - R 28 - Arg-Gln-Gln-Gly-Glu-R 34 -Asn-Gln-Glu-R 38 R 39 -R 40 -Arg-R 42 -R 43 -R 44 wherein R, is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His, which has either a Ca Me or Na Me substitution or is unsubstituted; R 2 is Ala or D-Ala; R 3 is Asp or D-Asp; R 8 is Ser, Asn, D-Ser or D-Asn; R 10 is Tyr or D-Tyr; R 12 is Arg or Lys; R, 3 is lie or Val; R 15 is Gly or D-Ala; R 17 is Leu or D-Leu; R 18 is Tyr or Ser; R23 is Leu or D-Leu; R 24 is His or Gin; R 25 is Glu, Asp, D-Glu or D-Asp; R 27 is Met, D-Met, Ala, Nle, lie, Leu, Nva or Val; R 28 is Asn or Ser; R 34 is Arg or Ser; R 38 is Gln or Arg; R39 is Arg or Gly; R 40 is Ser or Ala; R 42 is Phe, Ala or Val; R 43 is Asn or Arg; R 44 is a natural amino acid; provided however that either (a) R, has a Ca Me or an Na Me substitution or (b) R 17 and/or R 23 is D-Leu or (c) R 25 is either D-Glu or D-Asp and provided also that any or all of the residues between R 29 and R 44 , inclusive, may be deleted; or a nontoxic salt thereof. The C-terminus is preferably amidated. These peptides as well as nontoxic salts thereof may be administered to animals, including humans and cold-blooded animals, to stimulate the release of GH and may be used diagnostically. |