THE DEVELOPMENT AND APPLICATION OF TARGETABLE REACTIVE ELECTROPHILES AND OXIDANTS ("T-REX") TOWARD THE DISCOVERY OF NOVEL REDOX SENSOR PROTEINS

Abstract

Redox signaling has developed into a burgeoning field underpinning cellular signaling pathways important for health; the dysfunction of these pathways contributes to various diseases including cancers, neurodegenerative diseases, and diabetes, among others. These unique signaling processes are also shown to underlie development and aging pathways but the molecular mechanisms through which redox signals elicit their effects are largely unknown. Here we showcase the development and application of T-REX, a novel chemical biology tool, toward the discovery of novel redox sensor proteins in the model organism C. elegans. We also developed a method for evaluation of the on-target delivery of a variety of electrophiles onto WDR-23 and their effects on SKN-1, a key regulator of C. elegans antioxidant response pathway activation.