Work

Redox-based reagents for chemoselective methionine bioconjugation

Year: 2017

Type: article

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.

Source: Science

DOI: 10.1126/science.aal3316

Authors: Shixian Lin, Xiaoyu Yang, Shang Jia, Amy M. Weeks, Michael Hornsby, Peter S. Lee, Rita V. Nichiporuk, Anthony T. Iavarone, James A. Wells, F. Dean Toste, Christopher J. Chang

Institutions: University of California, Berkeley, ShanghaiTech University, University of California, San Francisco, QB3, Lawrence Berkeley National Laboratory, Howard Hughes Medical Institute

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Howard Hughes Medical Institute, U.S. Department of Energy, Helen Hay Whitney Foundation, National Institutes of Health, University of California, Davis, National Cancer Institute, National Institute of General Medical Sciences, Lawrence Berkeley National Laboratory

Awards: G1079818582, G1143651532, G1286236842, High Definition Ion Mobility Spectrometer, G2947551569, G3083819904, G382641700, G42916606, G5097698470, Discovery of immunotherapeutic biologics against the RAS-driven extracellular proteome, G6608191692, G7354628648, G7451908516, Chemical Probes to Study Copper Biology, G969889393

OpenAlex ID: W2593943479

FWCI: 17.57

Cites: 67

Cited by: 514

Related to: 10