Cysteine-reactive chemical probes based on a modular 4-aminopiperidine scaffold

Abstract

We utilized tri-functionalized 4-aminopiperidine as a modular scaffold to generate a cysteine-reactive probe library. Using in-gel fluorescence screening against lysates overexpressing glutathione S-transferase omega 1 (GSTO1) and the protein kinase AKT1, we identified SMC-1 and SMC-8 as activity-dependent covalent modifiers of these enzymes. These compounds are ideal chemical probes to monitor enzyme activity in proteomes.