Thioester ligation using peptide hydrazides as crypto-thioesters

Abstract

A practical strategy for thioester ligation using peptide hydrazides as crypto-thioesters is reported. In the convergent ligation strategy of thioester ligation, the N-terminal amino group of the intermediate thioester peptide readily reacts with its C-terminal thioester moiety via head-to-tail cyclisation. So far, peptide hydrazide has not yet been used as a crypto-thioester in thioester ligation because it reacts with thioesters in the presence of silver ion. To address this issue, we use di-tert-butyl dicarbonate to selectively protect the C-terminal acyl hydrazide under acidic conditions. The robustness and easy operability of this strategy will expand the utility of thioester ligation in chemical protein synthesis.