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In Cellulo Generation of Fluorescent Probes for Live-Cell Imaging of Cylooxygenase-2 |
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| Authors: | Jatinder Kaur Atul Bhardwaj Frank Wuest |
| Affiliation: | 1. Department of Oncology, University of Alberta, Edmonton, AB, Canada Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada These authors contributed equally to this work.;2. Department of Oncology, University of Alberta, Edmonton, AB, Canada |
| Abstract: | Live-cell imaging with fluorescent probes is an essential tool in chemical biology to visualize the dynamics of biological processes in real-time. Intracellular disease biomarker imaging remains a formidable challenge due to the intrinsic limitations of conventional fluorescent probes and the complex nature of cells. This work reports the in cellulo assembly of a fluorescent probe to image cyclooxygenase-2 (COX-2). We developed celecoxib-azide derivative 14 , possessing favorable biophysical properties and excellent COX-2 selectivity profile. In cellulo strain-promoted fluorogenic click chemistry of COX-2-engaged compound 14 with non/weakly-fluorescent compounds 11 and 17 formed fluorescent probes 15 and 18 for the detection of COX-2 in living cells. Competitive binding studies, biophysical, and comprehensive computational analyses were used to describe protein-ligand interactions. The reported new chemical toolbox enables precise visualization and tracking of COX-2 in live cells with superior sensitivity in the visible range. |
| Keywords: | cancer drug design fluorescence fluorogenic click chemistry imaging agents live cell imaging |