Expressed Protein Ligation at Methionine: N‐Terminal Attachment of Homocysteine, Ligation, and Masking

Abstract

A useful handle: One major limitation of protein semi-synthesis is the need for Cys at the ligation site in native chemical ligation reactions. It is shown that a transferase enzyme can deliver homocysteine to the N-terminus of an expressed protein (see scheme). Homocysteine can be used in a ligation reaction and then converted to Met. This allows one to use the MetArg or MetLys motif as a point of disconnection in semi-synthesis.