Improvement of Transpeptidative Protein Ligation via Selective Nucleophile Quenching using 2-Cyano-6-hydroxybenzothiazole
Here, we report a new method that employs a simple and readily available small molecule, 2-cyano-6-hydroxybenzothiazole (CBT), to selectively quench the nucleophilicity of an N-terminal Cys-containing leaving group, thereby shifting the equilibrium of peptidyl asparaginyl ligase (PAL)-mediated ligation toward the product side. This method can be applied not only to the N- and C-terminal modifications of proteins but also to efficiently mediate protein-protein ligation.
Authors
- Junyou Chen (ORCID: https://orcid.org/0000-0003-2631-6030)
- Tingting Cui (ORCID: https://orcid.org/0000-0001-6685-9457)
- Yincui Wu
- Guo‐Chao Chu (ORCID: https://orcid.org/0000-0003-2785-3399)
- Na Liu (ORCID: https://orcid.org/0000-0002-0333-1353)
- Jiaying Li (ORCID: https://orcid.org/0000-0002-1946-6156)
- Yang Xu (ORCID: https://orcid.org/0000-0002-8393-6255)
- Yi-Ming Li (ORCID: https://orcid.org/0000-0002-2161-2482)
Institutions
- University of Science and Technology of China (CN)
- Hefei University of Technology (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-03-25
- DOI
- https://doi.org/10.1021/acs.orglett.5c01007
- Citations
- 2
- Primary Topic
- Biochemical and Structural Characterization
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Anhui Province
- Fundamental Research Funds for the Central Universities