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Single-Molecule Observation of Intermediates in Bioorthogonal 2-Cyanobenzothiazole Chemistry |
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| Authors: | Dr Yujia Qing Mira D Liu Denis Hartmann Dr Linna Zhou Dr William J Ramsay Prof Hagan Bayley |
| Institution: | 1. Department of Chemistry, University of Oxford, Oxford, OX1 3TA UK;2. Department of Chemistry, University of Oxford, Oxford, OX1 3TA UK
W. M. Keck Science Department, Claremont McKenna College, Claremont, CA, 91711 USA Present address: Department of Chemistry, University of California, Berkeley, CA, 94720-1460 USA |
| Abstract: | We report a single-molecule mechanistic investigation into 2-cyanobenzothiazole (CBT) chemistry within a protein nanoreactor. When simple thiols reacted reversibly with CBT, the thioimidate monoadduct was approximately 80-fold longer-lived than the tetrahedral bisadduct, with important implications for the design of molecular walkers. Irreversible condensation between CBT derivatives and N-terminal cysteine residues has been established as a biocompatible reaction for site-selective biomolecular labeling and imaging. During the reaction between CBT and aminothiols, we resolved two transient intermediates, the thioimidate and the cyclic precursor of the thiazoline product, and determined the rate constants associated with the stepwise condensation, thereby providing critical information for a variety of applications, including the covalent inhibition of protein targets and dynamic combinatorial chemistry. |
| Keywords: | bioorthogonal chemistry click chemistry nanoreactors single-molecule studies tetrahedral intermediates |