Synthesis of peptide alpha-thioesters

摘要

Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide alpha thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an alpha-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide alpha-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.