Chemoselective Tyrosine Bioconjugation through Sulfate Click Reaction

Abstract

A novel and selective tyrosine functionalization strategy through SuFEx (sulfur fluoride exchange) chemistry is presented. In this approach, free tyrosine (Tyr) reacts selectively with aryl fluorosulfate in the presence of various nucleophilic amino acid residues in bio-tolerable conditions. Chemoselectivity of this unique SuFEx reaction was confirmed in amino acid, peptide, and protein conjugations. The functions of peptides and proteins were well-preserved as demonstrated from the Tyr-specific modification of cell-penetrating peptide and erythropoietin. This method is well-suited for residue-specific modification of native proteins, and thus would expand the versatility of bio-conjugation in protein chemistry.

Keywords: SuFEx; bioconjugation; chemoselectivity; fluorosulfate; tyrosine.