Substrate-Competitive Activity-Based Profiling of Ester Prodrug Activating Enzymes.

ABSTRACT: Understanding the mechanistic basis of prodrug delivery and activation is critical for establishing species-specific prodrug sensitivities necessary for evaluating preclinical animal models and potential drug-drug interactions. Despite significant adoption of prodrug methodologies for enhanced pharmacokinetics, functional annotation of prodrug activating enzymes is laborious and often unaddressed. Activity-based protein profiling (ABPP) describes an emerging chemoproteomic approach to assay active site occupancy within a mechanistically similar enzyme class in native proteomes. The serine hydrolase enzyme family is broadly reactive with reporter-linked fluorophosphonates, which have shown to provide a mechanism-based covalent labeling strategy to assay the activation state and active site

SUBMITTER: Xu H 

PROVIDER: S-EPMC4694564 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature