Strategies for Tuning the Selectivity of Chemical Probes that Target Serine Hydrolases

摘要: Summary Serine hydrolases comprise a large family of enzymes that have diverse roles in key cellular processes, such as lipid metabolism, cell signaling, and regulation post-translation modifications proteins. They are also therapeutic targets for multiple human pathologies, including viral infection, diabetes, hypertension, Alzheimer disease; however, few well-defined substrates biological functions. Activity-based probes (ABPs) been used effective tools to both profile activity screen selective inhibitors serine hydrolases. One broad-spectrum ABP containing fluorophosphonate electrophile has extensively advance our understanding Due the success this single reagent, several robust chemistries developed further diversify tune selectivity ABPs target In review, we highlight approaches identify hydrolase suggest new synthetic methodologies could be applied probe development.