Redox-based reagents for chemoselective methionine bioconjugation.

TitleRedox-based reagents for chemoselective methionine bioconjugation.
Publication TypeJournal Article
Year of Publication2017
AuthorsLin, Shixian, Yang Xiaoyu, Jia Shang, Weeks Amy M., Hornsby Michael, Lee Peter S., Nichiporuk Rita V., Iavarone Anthony T., Wells James A., F Toste Dean, and Chang Christopher J.
Date Published2017 Feb 10

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.

Alternate JournalScience
PubMed ID28183972

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