Synthesis of hGRF (somatocrinin) in liquid phase and intermediate peptides

摘要

A process for the synthesis, in liquid phase and by fragments, of hGRF 1-44 and hGRF 1-40. This process consists in coupling, one after the other and in the order of the sequence of the GRF, (1) on the one hand, the following fragments: -H-Ala-Arg-Ala-Arg-Leu-NH2 called hGRF - Frag- (40-44) or - ment A alaninamide - (40) -H-Gln-Glu-Arg-Gly-OH called hGRF - Frag- (36-39) - ment B'1 -H-Glu-Ser-Asn-OH called hGRF - Frag- (33-35) - ment B'2 -H-Ser-Arg-Gln-Gln-Gly-OH called hGRF - Frag- (28-32) - ment C -H-Leu-Gln-Asp-Ile-Met-OH called hGRF - Frag- (23-27) - ment D' -H-Arg-Lys-Leu-OH called hGRF - Frag- (20-22) - ment E'1 - to obtain the peptide K1 [(hGRF (20-44)] on the corresponding peptide having the sequence (20-40) and (2) on the other hand, the following fragments: -H-Gln-Leu-Ser-Ala called hGRF - Frag- (16-19) - ment F1 -H-Tyr-Arg-Lys-Val-Leu-Gly OH called hGRF - Frag- (10-15) - ment G1 -H-Ile-Phe-Thr-Asn-Ser-OH called hGRF - Frag- (5-9) - ment H1 - to obtain the peptide J [hGRF (5-19)] and thereafter to couple together the peptides J and K1 in order to form the peptide having the sequence hGRF (5-44) or hGRF (5-40) and finally to couple the resulting peptide with the peptide H-Tyr-Ala-Asp-Ala-H, called fragment I hGRF (1-4).