Activity-based protein profiling (ABPP) is a powerful technique to identify enzymatic activities and to study their functioning - and the effect of inhibitors on this - in vitro, in situ, and in vivo. In this chapter some case studies on activity-based profiling of mammalian proteasomes are discussed. Both direct and two-step bioorthogonal ABPP strategies and their merits are discussed, and the value of ABPP in the establishment of previously uncharted enzymatic activities and the direct visualization of inhibitor specificity are presented. Proteasomes are essential factors in the detection and eradication of virally infected cells. Besides their fundamental interest, proteasomes are relevant therapeutic targets. Proteasomes are useful targets in the development of chemical biology research strategies, and in return chemical biology approaches help in establishing proteasome activities in health and disease and in determining their relevance as drug targets.
- Activity-based proteasome profiling (ABPP)
- Chemical biology
- Medicinal chemistry