Chemoselective Copper-Mediated Modification of Selenocysteines in Peptides and Proteins.

Abstract

Highly valuable bioconjugated molecules must be synthesized through efficient, chemoselective chemical modifications of peptides and proteins. Herein, we report the chemoselective modification of peptides and proteins via a reaction between selenocysteine residues and aryl/alkyl radicals. In situ radical generation from hydrazine substrates and copper ions proceeds rapidly in an aqueous buffer at near neutral pH (5-8), providing a variety of Se-modified linear and cyclic peptides and proteins conjugated to aryl and alkyl molecules, and to affinity label tag (biotin). This chemistry opens a new avenue for chemical protein modifications.