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[Research Article] Redox-based reagents for chemoselective methionine bioconjugation

ScienceNOW - Fetched: February 9th, 2017, 3:00pm UTC

Cysteine can be specifically functionalized by a myriad of acid-base conjugation strategies for applications ranging from probing protein function to antibody-drug conjugates and proteomics. In contrast, selective ligation to the other sulfur-containing amino acid, methionine, has been precluded by its intrinsically weaker nucleophilicity. Here, we report a strategy for chemoselective methionine bioconjugation through redox reactivity, using oxaziridine-based reagents to achieve highly selective, rapid, and robust methionine labeling under a range of biocompatible reaction conditions. We highlight the broad utility of this conjugation method to enable precise addition of payloads to proteins, synthesis of antibody-drug conjugates, and identification of hyperreactive methionine residues in whole proteomes. Authors: Shixian Lin, Xiaoyu Yang, Shang Jia, Amy M. Weeks, Michael Hornsby, Peter S. Lee, Rita V. Nichiporuk, Anthony T. Iavarone, James A. Wells, F. Dean Toste, Christopher J. Chang

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