Solid‐phase synthesis of somatostatin and glucagon‐selective analogs in gram quantities

Abstract

Abstract Somatostatin (SS) and two glucagon selective analogs [ D ‐Cys l4 ]‐SS and [ D ‐Trp 8 , D ‐Cys 14 ]‐SS have been synthesized in gram quantities by the solid‐phase procedure. A general modification of Monahan and Gilon's procedure for esterification of the first protected amino acid onto the chloromethylated resin as well as a general protocol for solid‐phase peptide synthesis on Beckman 990 automatic synthesizer are described. A new general procedure for disulfide formation, which involves the adaptation of the “high‐dilution” principle to the ferricyanide oxidation and the optimization of the sequence of purification steps as applied to somatostatin and its analogs, yields highly purified peptides (≥ 199% pure) as checked by reverse‐phase high‐pressure liquid chromatography—which is shown to be a highly sensitive, resolutive, and quantitative analytical tool for evaluation of the homogeneity of peptides.