Oxidative deselenization of selenocysteine: Applications for programmed ligation at serine

Despite the unique chemical properties of selenocysteine (Sec), ligation at Sec is an under-utilized methodology for protein synthesis. We describe herein an unprecedented protocol for the conversion of Sec to serine (Ser) in a single, high-yielding step. When coupled with ligation at Sec, this transformation provides a new approach to programmed ligations at Ser residues. This new reaction is compatible with a wide range of functionality, including the presence of unprotected amino acid side chains and appended glycans. The utility of the methodology is demonstrated in the rapid synthesis of complex glycopeptide fragments of the epithelial glycoproteins MUC5AC and MUC4 and through the total synthesis of the structured, cysteine (Cys)-free protein eglin C. An operationally simple method for the rapid and chemoselective conversion of selenocysteine (Sec) to serine (Ser) in aqueous media is described. This mechanistically distinct transformation at selenium facilitates the synthesis of complex peptides and proteins, as highlighted in the synthesis of fragments of the epithelial glycoproteins MUC5AC and MUC4 and in the total synthesis of the serine protease inhibitor eglin C.