Chemoselective Stabilized Triphenylphosphonium Probes for Capturing Reactive Carbonyl Species and Regenerating Covalent Inhibitors with Acrylamide Warheads in Cellulo.

ABSTRACT: Reactive carbonyl species (RCS) are important biomarkers of oxidative stress-related diseases because of their highly reactive electrophilic nature. Despite their potential as triggers for prodrug activation, selective labeling approaches for RCS remain limited. Here, we utilized triphenylphosphonium groups to chemoselectively capture RCS via an aqueous Wittig reaction, forming α,β-unsaturated carbonyls that enable further functionalization. We first designed native (light) and deuterated (heavy) probes to facilitate RCS metabolomic identification through distinct MS isotope patterns. This approach allowed us to capture and relatively quantify several endogenous RCS related to advanced lipoxidation/glycation end products (ALEs/AGEs). Second, we demonstrated that various endogenous RCS can

SUBMITTER: Chen AL 

PROVIDER: S-EPMC11744745 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature