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 Fragment A hGRF (40-44) or - alaninamide (40) -H-Gln-Glu-Arg-Gly-OH called Fragment B'1 hGRF (36-39) -H-Glu-Ser-Asn-OH called Fragment B'2 hGRF (33-35) -H-Ser-Arg-Gln-Gln-Gly-OH called Fragment C hGRF (28-32) -H-Leu-Gln-Asp-Ile-Met-OH called Fragment D' hGRF (23-27) -H-Arg-Lys-Leu-OH called Fragment E'1 hGRF (20-22) - 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 Fragment F1 hGRF (16-19) -H-Tyr-Arg-Lys-Val-Leu-Gly OH called Fragment G1 hGRF (10-15) -H-Ile-Phe-Thr-Asn-Ser-OH called Fragment H1 hGRF (5-9) - 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-OH, called fragment I hGRF (1-4).