Citation: Jingrong Huang, Xin Ding, Zihan Lin, Yu Lin, Yongqi Liao, Wang Gu, Fa-Jie Chen, Fen-Er Chen. Bromo nitrile oxide-mediated disulfide formation and capping of N-terminal cysteine in peptides[J]. Chinese Chemical Letters, ;2026, 37(6): 111715. doi: 10.1016/j.cclet.2025.111715 shu

Bromo nitrile oxide-mediated disulfide formation and capping of N-terminal cysteine in peptides

Jingrong Huang ^a ,
Xin Ding ^a ,
Zihan Lin ^a ,
Yu Lin ^a ,
Yongqi Liao ^a ,
Wang Gu ^a ,
Fa-Jie Chen ^{a, *,} ,
Fen-Er Chen ^{a, b, c, *,}

a.
Key Laboratory of Molecule Synthesis and Function Discovery (Fujian Province University), College of Chemistry, Fuzhou University, Fuzhou 350108, China
b.
Department of Chemistry, Engineering Center of Catalysis and Synthesis for Chiral Molecules, Fudan University, Shanghai 200433, China
c.
Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, China

fajie.chen@fzu.edu.cn

rfchen@fudan.edu.cn

Received Date: 6 May 2025
Revised Date: 30 July 2025
Accepted Date: 12 August 2025
Available Online: 13 August 2025

Figures(6)

Nitrile oxide is a highly reactive species used for organic synthesis and bioconjugation. Herein, we developed a novel approach for disulfide formation and capping of N-terminal cysteine in peptides mediated by bromo nitrile oxide. 1,1-Dibromoformaldoxime acts as the precursor for bromo nitrile oxide. This transformation proceeds under mild conditions with rapid kinetics, efficiently converting a broad range of thiophenols, thiols, and cysteine-containing native peptides into disulfides, cyclic disulfides, or thiazolidin-2-one oximes. Notably, oxidant-sensitive residues such as methionine, tyrosine, and tryptophan are well tolerated without over-oxidation. The compatibility with aqueous media further highlights its potential for the late-stage modification of native peptides and the derivatization of biologically active molecules.
- Nitrile oxide,
- Disulfide,
- Cysteine,
- Thiol,
- N-Terminus modification,
- Peptide
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