Redox-based reagents for chemoselective methionine bioconjugation
- Science. 2017 Feb 10;355(6325):597-602. doi: 10.1126/science.aal3316.
- 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. [email protected] [email protected].
- 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.
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.