Investigating cysteine‐mediated protein activities in complex proteomes

Abstract

Cysteine residues on proteins have important catalytic and regulatory roles in complex proteomes. Chemical probes and mass spectrometry-based proteomics can be used to investigate proteins that possess these reactive cysteines, to better understand their reactivity and role in disease. Development of a probe library that is specifically tuned for reactive cysteines is essential. Using a piperidine scaffold, we are able to incorporate a cysteine-specific electrophile, alkyne reporter group and binding groups to develop a library of probes that can be used for Activity Based Protein Profiling (ABPP). We have employed these techniques to identify proteins such as Cathepsin D and Protein Kinase B (AKT1) and have begun to study their activities as well as their roles in cancer