2. Academic Validation
  3. Wittig reagents for chemoselective sulfenic acid ligation enables global site stoichiometry analysis and redox-controlled mitochondrial targeting

Wittig reagents for chemoselective sulfenic acid ligation enables global site stoichiometry analysis and redox-controlled mitochondrial targeting

  • Nat Chem. 2021 Nov;13(11):1140-1150. doi: 10.1038/s41557-021-00767-2.
Yunlong Shi 1,  Ling Fu 2 3 4,  Jing Yang 5 6 7,  Kate S Carroll 8
Affiliations

Affiliations

  • 1 Department of Chemistry, The Scripps Research Institute, Jupiter, FL, USA.
  • 2 State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing, China.
  • 3 National Center for Protein Sciences-Beijing, Beijing, China.
  • 4 Beijing Institute of Lifeomics, Beijing, China.
  • 5 State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing, China. yangjing@ncpsb.org.cn.
  • 6 National Center for Protein Sciences-Beijing, Beijing, China. yangjing@ncpsb.org.cn.
  • 7 Beijing Institute of Lifeomics, Beijing, China. yangjing@ncpsb.org.cn.
  • 8 Department of Chemistry, The Scripps Research Institute, Jupiter, FL, USA. kcarroll@scripps.edu.
PMID: 34531572 DOI: 10.1038/s41557-021-00767-2
Abstract

Triphenylphosphonium ylides, known as Wittig reagents, are one of the most commonly used tools in synthetic chemistry. Despite their considerable versatility, Wittig reagents have not yet been explored for their utility in biological applications. Here we introduce a chemoselective ligation reaction that harnesses the reactivity of Wittig reagents and the unique chemical properties of sulfenic acid, a pivotal post-translational cysteine modification in redox biology. The reaction, which generates a covalent bond between the ylide nucleophilic α-carbon and electrophilic γ-sulfur, is highly selective, rapid and affords robust labelling under a range of biocompatible reaction conditions, which includes in living cells. We highlight the broad utility of this conjugation method to enable site-specific proteome-wide stoichiometry analysis of S-sulfenylation and to visualize redox-dependent changes in mitochondrial cysteine oxidation and redox-triggered triphenylphosphonium generation for the controlled delivery of small molecules to mitochondria.

Figures
Products