Anuj K. Yadav, Christopher J. Reinhardt, Andres S. Arango, Hannah C. Huff,
Liang Dong, Michael G. Malkowski, Aditi Das, Emad Tajkhorshid, and Jefferson
Chan.
An activity-based sensing approach for the detection of
cyclooxygenase-2 in live cells.
Angewandte Chemie - International Edition in English,
132:2-10, 2019.
YADA2019-ET
Cyclooxygenase-2 (COX-2) overexpression is prominent in
inflammatory diseases, neurodegenerative disorders, and cancer.
Directly monitoring COX-2 activity within its native environment
poses an exciting approach to account for and illuminate the
effect of the local environments on protein activity. Herein, we
report the development of CoxFluor, the first activity-based
sensing approach for monitoring COX-2 within live cells with
confocal microscopy and flow cytometry. CoxFluor strategically
links a natural substrate with a dye precursor to engage both the
cyclooxygenase and peroxidase activities of COX-2. This catalyzes
the release of resorufin and the natural product, as supported by
molecular dynamics and ensemble docking. CoxFluor enabled the
detection of oxygen-dependent changes in COX-2 activity that are
independent of protein expression within live macrophage cells.
