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

Abstract

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.

Supplementary files

Article information

Article type
Communication
Submitted
31 Mar 2025
Accepted
04 Jun 2025
First published
04 Jun 2025
This article is Open Access
Creative Commons BY license

Chem. Commun., 2025, Accepted Manuscript

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

J. W. van den Heuvel, E. O. Olaniran Håkansson, B. Skillinghaug and L. R. Odell, Chem. Commun., 2025, Accepted Manuscript , DOI: 10.1039/D5CC01813G

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