Discovery of a Redox-activatable chemical probe for detection of cyclooxygenase-2 in cells and animals
Date
2022-07-15Author
Uddin, Md. Jashim
Lo, Justin Han-Je
Oltman, Connor G.
Crews, Brenda C.
Huda, Tamanna
Liu, Justin
Kingsley, Philip J.
Lin, Shuyang
Milad, Mathew
Aleem, Ansari M.
Asaduzzaman, Abu
McIntyre, J. Oliver
Duvall, Craig L.
Marnett, Lawrence J.
Metadata
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Uddin, M. J., Lo, J. H.-J., Oltman, C. G., Crews, B. C., Huda, T., Liu, J., . . . Marnett, L. J. (2022). Discovery of a Redox-Activatable Chemical Probe for Detection of Cyclooxygenase-2 in Cells and Animals. ACS Chemical Biology, 17(7), 1714-1722. https://doi.org/10.1021/acschembio.1c00961
Abstract
Cyclooxygenase-2 (COX-2) expression is up-regulated in inflammatory tissues and many premalignant and malignant tumors. Assessment of COX-2 protein in vivo, therefore, promises to be a powerful strategy to distinguish pathologic cells from normal cells in a complex disease setting. Herein, we report the first redox-activatable COX-2 probe, fluorocoxib Q (FQ), for in vivo molecular imaging of pathogenesis. FQ inhibits COX-2 selectively in purified enzyme and cell-based assays. FQ exhibits extremely low fluorescence and displays time- and concentration-dependent fluorescence enhancement upon exposure to a redox environment. FQ enters the cells freely and binds to the COX-2 enzyme. FQ exhibits high circulation half-life and metabolic stability sufficient for target site accumulation and demonstrates COX-2-targeted uptake and retention in cancer cells and pathologic tissues. Once taken up, it undergoes redox-mediated transformation into a fluorescent compound fluorocoxib Q-H that results in high signal-to-noise contrast and differentiates pathologic tissues from non-pathologic tissues for real-time in vivo imaging.
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