Synthetic analogs of growth hormone releasing factor

Details Synthetic analogs of growth hormone releasing factor Synthetic analogs of growth hormone releasing factor

C - Chemistry, Metallurgy

07

K

530/7.1

C07K 14/60 (2006.01) A23K 1/16 (2006.01) A61K 38/00 (2006.01)

Patent

CA 1271299

ABSTRACT OF THE DISCLOSURE Human GRF(hGRF), rat GRF(rGRF) porcine GRF(pGRF) and bovine GRF(bGRF) 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 have the sequence: R1-R2-R3-Ala-Ile-Phe-Thr-R8-Ser -R10-Arg-R12- R13-R14-R15-Gln-R17-R18-Ala-Arg-Lys-Leu-R23- R24-R25-Ile-R27-R28-R29-Gln-Gln-Gly-Glu-R34- Asn-Gln-Glu-R38-R39-R40-Arg-R42-R43-R44 wherein R1 is Tyr, D-Tyr, Met, Phe, D-Phe, pC1-Phe, Leu, His or D-His having either a C?Me or N?Me substitution or being unsubstituted; R2 is Ala, D-Ala or D-NMA; R3 is Asp or D-Asp; R8 is Ser, Asn, D-Ser or D-Asn; R10 is Tyr or D-Tyr; R12 is Arg or Lys; R13 is Ile or Val; R14 is Leu or D-Leu; R15 is Gly or D-Ala; R17 is Leu or D-Leu; R18 is Tyr or Ser; R23 is Leu or D-Leu; R24 is His or Gln; R25 is Glu, Asp, D-Glu or D-Asp; R27 is Met, D-Met, Ala, Nle, Ile, Leu, Nva or Val; R28 is Asn or Ser; R29 is Arg or D-Arg; R34 is Arg or Ser; R38 is Gln or Arg; R39 is Arg or Gly; R40 is Ser or Ala; R42 is Phe, Ala or Val; R43 is Asn or Arg; R44 is a natural amino acid; provided however that any or all of the residues between R28 and R44, inclusive, may be deleted and provided also that R2 is D-NMA and/or R14 is D-Leu and/or R29 is D-Arg. These peptides as well as their nontoxic salts may also be used diagnostically.

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