Improvement of Transpeptidative Protein Ligation via Selective Nucleophile Quenching using 2-Cyano-6-hydroxybenzothiazole

• DOI: 10.1021/acs.orglett.5c01007
• Publication Date: 2025-03-25T09:17:28Z
• Authors: Junyou Chen; Junjiang Li; Tingting Cui; Na Liu; Yincui Wu; Yang Xu; Guo-Chao Chu; Yi-Ming Li

Here, we report a new method that employs 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 equilibrium peptidyl asparaginyl ligase (PAL)-mediated ligation toward product side. This can be applied not only N- C-terminal modifications proteins but also efficiently mediate protein-protein ligation.