Chemistry‐Driven Approaches to Deconstruct Redox‐Linked Signal Transduction Networks

Abstract

Oxidative and electrophilic stress that results from loss of redox homeostasis has become increasingly appreciated to underlie numerous disease states including inflammation, cardiovascular disease, cancer, neurodegeneration, and psychiatric disorders. Utilizing our novel T‐REX (Targeted Reactive Electrophiles and oXidants) methodology, we aim to better resolve electrophile‐ and oxidant‐mediated signaling effects on any protein of interest (POI). In contrast to widely used methodologies, in which live specimens are treated globally with inherently reactive electrophiles and oxidants (RES/ROS) in excess quantities, our technique allows us to selectively deliver these reactive species to specific POIs with spatiotemporal control. Herein, T‐REX is exploited to delineate the functional consequences of H2O2 signaling along individual disease relevant redox‐dependent pathways in live cells and animals.