Catalytic covalent inhibition of cyclooxygenase-1 by a biomimetic acyltransferase
Wei Bao1, Baruch Turniansky1, John Koh1
1University of Delaware, 102 Brown Laboratory, Newark, DE 19716, USA.
Abstract:
Covalent binding enzyme inhibitors have grown in acceptance in therapeutic discovery. Several recent examples of protein-targeting acyl-transfer catalysts covalently modify protein targets in cellular systems but generally do not affect protein function. In this study, a small molecule has been developed for the first time that can achieve catalytic covalent inhibition of the inflammatory response enzyme, cyclooxygenase-1, in cells using only endogenous acetyl-CoA as a co-substrate. By utilizing a catalytic inhibitor which can self-regenerate, a sustained inhibitory response is achieved in cells compared to the analogous non-catalytic covalent cyclooxygenase antagonist, acetylsalicylic acid (aspirin).
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