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Redox-based reagents for chemoselective methionine bioconjugation.

ABSTRACT: 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.

SUBMITTER: Lin S

PROVIDER: S-EPMC5827972 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Redox-based reagents for chemoselective methionine bioconjugation.

Lin Shixian S Yang Xiaoyu X Jia Shang S Weeks Amy M AM Hornsby Michael M Lee Peter S PS Nichiporuk Rita V RV Iavarone Anthony T AT Wells James A JA Toste F Dean FD Chang Christopher J CJ

Science (New York, N.Y.) 20170201 6325

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 ...[more]

PMID: 28183972

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