One-pot, chemoselective desulfurative functionalization of cysteine containing peptides using pyridinium salts.

Peptide and protein modifications, especially late-stage derivatization, are invaluable for the synthesis of new pharmaceuticals. Currently, cysteine-mediated peptide modification is mainly limited to bioconjugation and disulfide formation. Therefore, exploration of new cysteine mediated peptide modifications is of great interest. Herein, we present a practical strategy for the three-step, one-pot desulfurative functionalization of cysteine containing peptides. The use of a pyridinium salt enables diverse and selective functionalization with an array of nucleophiles such as amino acid side chains, pharmaceuticals and macrocyclizations. This method allows for easy and diverse late-stage modification of peptides enabling the discovery and synthesis of new pharmaceuticals.