Advanced search
1 file | 1.08 MB Add to list

Thiol-thiol cross-clicking using bromo-ynone reagents

Marvin Nicque (UGent) , Jan H. Meffert (UGent) , Diederick Maes (UGent) , Kevin Bevernaege, Mehwish Iftikhar (UGent) , Olivier Zwaenepoel (UGent) , Jan Gettemans (UGent) , Annemieke Madder (UGent) and Johan Winne (UGent)
Author
Organization
Project
Abstract
Thiols are used in many click reactions, and are also excellent platforms for biomolecular click or bioconjugation reactions. The direct cross-coupling of two thiols is an attractive biomimetic concept for click chemistry, but leads to statistical mixtures of homo- and heterodimers. Here, we introduce a novel class of thiol-click reagents, bromo-ynones, where the kinetic differentiation between the first and second thiol addition onto these reagents facilitates a stepwise one-pot cross-clicking of two distinct thiols in aqueous media, without the need for intermediate isolation or purification. The two thiols are linked through a single carbon atom, mimicking a disulfide bridge. We demonstrate the use of bromo-ynones in the synthesis of various cross-coupled thiols, including small molecule drugs, fluorophores, carbohydrates, peptides and proteins, including an example of a protein-protein heterodimer. The resulting adducts are robust under physiological conditions and by judicious choice of the bromo-ynone reagent, the adducts can be stable even in the presence of excess free thiols.
Keywords
BIOCONJUGATION, CHEMISTRY, CYCLOADDITION, STABILIZATION, PEPTIDES, LINKERS, ALKYNES, PHASE, ACID

Downloads

  • publisher version.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 1.08 MB

Citation

Please use this url to cite or link to this publication:

MLA
Nicque, Marvin, et al. “Thiol-Thiol Cross-Clicking Using Bromo-Ynone Reagents.” NATURE COMMUNICATIONS, vol. 16, no. 1, 2025, doi:10.1038/s41467-025-61682-5.
APA
Nicque, M., Meffert, J. H., Maes, D., Bevernaege, K., Iftikhar, M., Zwaenepoel, O., … Winne, J. (2025). Thiol-thiol cross-clicking using bromo-ynone reagents. NATURE COMMUNICATIONS, 16(1). https://doi.org/10.1038/s41467-025-61682-5
Chicago author-date
Nicque, Marvin, Jan H. Meffert, Diederick Maes, Kevin Bevernaege, Mehwish Iftikhar, Olivier Zwaenepoel, Jan Gettemans, Annemieke Madder, and Johan Winne. 2025. “Thiol-Thiol Cross-Clicking Using Bromo-Ynone Reagents.” NATURE COMMUNICATIONS 16 (1). https://doi.org/10.1038/s41467-025-61682-5.
Chicago author-date (all authors)
Nicque, Marvin, Jan H. Meffert, Diederick Maes, Kevin Bevernaege, Mehwish Iftikhar, Olivier Zwaenepoel, Jan Gettemans, Annemieke Madder, and Johan Winne. 2025. “Thiol-Thiol Cross-Clicking Using Bromo-Ynone Reagents.” NATURE COMMUNICATIONS 16 (1). doi:10.1038/s41467-025-61682-5.
Vancouver
1.
Nicque M, Meffert JH, Maes D, Bevernaege K, Iftikhar M, Zwaenepoel O, et al. Thiol-thiol cross-clicking using bromo-ynone reagents. NATURE COMMUNICATIONS. 2025;16(1).
IEEE
[1]
M. Nicque et al., “Thiol-thiol cross-clicking using bromo-ynone reagents,” NATURE COMMUNICATIONS, vol. 16, no. 1, 2025.
@article{01K21RNYNQ0TRRVAH8NWWBCTFV,
  abstract     = {{Thiols are used in many click reactions, and are also excellent platforms for biomolecular click or bioconjugation reactions. The direct cross-coupling of two thiols is an attractive biomimetic concept for click chemistry, but leads to statistical mixtures of homo- and heterodimers. Here, we introduce a novel class of thiol-click reagents, bromo-ynones, where the kinetic differentiation between the first and second thiol addition onto these reagents facilitates a stepwise one-pot cross-clicking of two distinct thiols in aqueous media, without the need for intermediate isolation or purification. The two thiols are linked through a single carbon atom, mimicking a disulfide bridge. We demonstrate the use of bromo-ynones in the synthesis of various cross-coupled thiols, including small molecule drugs, fluorophores, carbohydrates, peptides and proteins, including an example of a protein-protein heterodimer. The resulting adducts are robust under physiological conditions and by judicious choice of the bromo-ynone reagent, the adducts can be stable even in the presence of excess free thiols.}},
  articleno    = {{6386}},
  author       = {{Nicque, Marvin and Meffert, Jan H. and Maes, Diederick and Bevernaege, Kevin and Iftikhar, Mehwish and Zwaenepoel, Olivier and Gettemans, Jan and Madder, Annemieke and Winne, Johan}},
  issn         = {{2041-1723}},
  journal      = {{NATURE COMMUNICATIONS}},
  keywords     = {{BIOCONJUGATION,CHEMISTRY,CYCLOADDITION,STABILIZATION,PEPTIDES,LINKERS,ALKYNES,PHASE,ACID}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{9}},
  title        = {{Thiol-thiol cross-clicking using bromo-ynone reagents}},
  url          = {{http://doi.org/10.1038/s41467-025-61682-5}},
  volume       = {{16}},
  year         = {{2025}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: