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.
JournalScience
Volume355
Issue6325
Pagination597-602
Date Published2017 02 10
ISSN1095-9203
KeywordsActins, Aziridines, Cysteine, Gene Editing, Gene Knockout Techniques, Immunoconjugates, Methionine, Mutation, Oxidation-Reduction, Phosphopyruvate Hydratase, Protein Domains, Proteins, Proteomics, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sodium Hypochlorite
Abstract

<p>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.</p>

DOI10.1126/science.aal3316
Alternate JournalScience
PubMed ID28183972
Grant ListP41 CA196276 / CA / NCI NIH HHS / United States
F32 CA203152 / CA / NCI NIH HHS / United States
R01 GM079465 / GM / NIGMS NIH HHS / United States
S10 OD020062 / OD / NIH HHS / United States

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