Insights into the finer issues of native chemical ligation: an approach to cascade ligations

Abstract

An efficient and broadly useful two-step ligation protocol is developed. Important mechanistic issues of ligation were probed from diastereomeric competition studies on the formation of the ligation products. We also report an instance of kinetically controlled ligation through the exploitation of selectivity differences between related N-termini. This study potentially provides a valuable approach to facilitate polypeptide synthesis by minimizing protecting group manipulations and intermediate isolations..