Grf analogs

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

530/7.1, 195/1.3

C07K 14/60 (2006.01) A61K 38/00 (2006.01)

Patent

CA 1299507

GRF ANALOGS ABSTRACT OF THE DISCLOSURE Human pancreatic GRF and the hypothalamic GRFs for the human and several other mammalian species were earlier characterized and synthesized. The invention provides synthetic peptides which are potent stimulators of the release of pituitary GH in animals, including humans, and which have the formula: R1-R2-R3-Ala- R5-R6-R7-R8-R9-R10-R11-R12-R13-Leu-R15-Gln-Leu-R18- R19-R20-R21-Leu-Leu-Gln-Glu-R26-R27-R28-Arg-Y wherein R1 is Tyr, D-Tyr, Met, Phe, D-Phe, Leu, His or D-His, which has either a CaMe or NaMe substitution or is unsubstituted; R2 is Ala or D-Ala; R3 is Asp or D-Asp; R5 is Ile or Leu; R6 is Phe or Tyr; R7 is Ser or Thr; R8 is Ser, Asn, Thr or Gln; R9 is Ala or Ser: R10 is Tyr, Phe or Leu; R11 in Arg, Orn or Lys; R12 is Arg, Orn or Lys; R13 is Ile, Leu, Phe or Val; R15 is Gly or Ala; R18 is Ala or Ser; R19 is Ser or Ala; R20 is Arg, Orn or Lys; R21 is Arg, Orn or Lys; R26 is Leu, Ile, Val or Phe; R27 is Nle, Nva or a natural amino acid; R28 is Ala, Leu, Asn, Gln, or Ser; and Y is OH or NH2; provided however that at least four of the residues constituting R5, R6, R7, R8, R9, R10, R11, R12, R13, R15, R18, R19, R20, R21 and R26 are different from the residues appearing in that respective position in the native molecule. 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.

514869

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