Active-site directed probes to report enzymatic action in the ubiquitin proteasome system.
Irreversible covalent inhibitors equipped with reporter groups, also termed activity-based probes, allow the study of target enzymes based on catalytic activity instead of expression level, which does not necessarily indicate protein function and subsequent cellular consequences. Activity-based probes offer advantages over traditional techniques: they can be applied to the cell or tissue of choice and molecular imaging and pharmacology applications are possible. Here the design and use of probes directed at enzymatic activities in the ubiquitin proteasome system are discussed. This system holds promise for the development of new, targeted anticancer therapies and the probes discussed here might aid in fulfilling this promise.
Ovaa
Huib
H
Division of Cellular Biochemistry, Netherlands Cancer Institute (NKI), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. h.ovaa@nki.nl
D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D015335:Molecular Probes; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D015335:Molecular Probes; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex