Sulfa-Michael Addition on Dehydroalanine: A Versatile Reaction for Protein Modifications.

Chemical modification of proteins has been widely applied in diagnostic and therapeutic processes. Here, we report a novel bioconjugation between sulfinic acids and amino acid dehydroalanine (Dha) in the context of both small molecules and proteins. This conjugation enables the rapid formation of sulfone linkages in a chemoselective and disulfide-compatible manner under biocompatible conditions with Dha residues chemically installed in proteins and thus provides a robust tool that is simple and has exquisite site selectivity for protein functionalization in a wide range.