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  3. Methionine-specific nonreversible bioconjugation: Advancing precision protein modification

Methionine-specific nonreversible bioconjugation: Advancing precision protein modification

  • Proc Natl Acad Sci U S A. 2026 Feb 17;123(7):e2519038123. doi: 10.1073/pnas.2519038123.
Shirui Wang # 1 2,  Zhenguo Zhang # 1 2,  Raymond Tio 2,  Bohan Li 2,  Joycelyn Yi Xin Khoo 2,  Teck-Peng Loh 1 2 3
Affiliations

Affiliations

  • 1 Department of Chemistry, School of Sciences, Great Bay University, Dongguan 523000, China.
  • 2 Division of Chemistry and Biological Chemistry, School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore.
  • 3 Henan Linker Technology Key Laboratory, College of Advanced Interdisciplinary Science and Technology, Henan University of Technology, Zhengzhou 450001, China.
  • # Contributed equally.
PMID: 41665996 DOI: 10.1073/pnas.2519038123
Abstract

We present a methionine-selective, nonreversible bioconjugation strategy that employs activated allylic bromides under mild, aqueous reaction conditions compatible with various peptides and proteins. Compared with conventional allylic bromides, our method improves conjugate stability and suppresses nonspecific reactivity under the examined reaction conditions. This method enables methionine-preferred labeling of peptides and proteins, and provides proof-of-concept applications in covalent inhibitor design and protein functionalization. As a complementary addition to existing methionine bioconjugation strategies, this chemistry expands the toolkit available for protein modification and chemical biology research.

Keywords

activated allylic bromide; late-stage modification; methionine bioconjugation; methionine specificity; mild conditions.

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