Analogs of human growth hormone-releasing hormone, their preparation and use

Abstract

Growth hormone-releasing hormone analogs having the amino acid sequence of the formula: Dat-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-R-R-VAL-Leu-Ala-Gln-Leu-Ser-Ala-R-R-Leu-Leu-Gln-Asp-Ile-Nle-Asp-R-NH(I), wherein Ris hArg, Gab or Gap; Ris hArg, Orn, Gab or Gap; Ris hArg, hArg, Gab or Gap; Ris hArg, Orn, Gab or Gap; Ris D-Arg, hArg, Gab or Gap; and their pharmaceutically acceptable salts. Said peptides are potent and selective stimulators of GH release and they are highly resistant to enzymatic degradation. Said peptides are prepared using the solid phase synthesis method, by introducing suitable derivatives of lysine, 2,4-diaminobutyric acid or 2,3-diaminopropionic acid at appropriate positions in the peptide chain attached to a polymeric support, deprotecting side-chain amino groups and reacting free amino groups with a guanidinating agent, removing all remaining t-butyloxycarbonyl protective groups, and cleaving the synthesized peptide from the support, followed by purification and optionally, converting the peptide into a pharmaceutically acceptable salt.