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Science. 2017 Feb 10;355(6325):597-602. doi: 10.1126/science.aal3316.

Redox-based reagents for chemoselective methionine bioconjugation.

Author information

1
Department of Chemistry, University of California, Berkeley, CA, USA.
2
School of Physical Science and Technology, ShanghaiTech University, Shanghai, China.
3
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
4
California Institute for Quantitative Biosciences, University of California, Berkeley, CA, USA.
5
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.
6
Department of Chemistry, University of California, Berkeley, CA, USA. chrischang@berkeley.edu fdtoste@berkeley.edu.
7
Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
8
Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
9
Howard Hughes Medical Institute, University of California, Berkeley, CA, USA.

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.

PMID:
28183972
PMCID:
PMC5827972
DOI:
10.1126/science.aal3316
[Indexed for MEDLINE]
Free PMC Article

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