Novel proteomics based method detects inhibition of intracellular deubiquitylating enzymes

Researchers at the University of Oxford and Progenra, Inc. are pleased to announce the publication of a research article entitled "Activity-Based Chemical Proteomics Accelerates Inhibitor Development for Deubiquitylating Enzymes" (Altun et al, Chemistry & Biology, Volume 18, Issue 11, 1401-1412, 23 November 2011) that details a novel proteomics based method to detect inhibition of intracellular deubiquitylating enzymes (DUBs). The new method utilizes LC-MS-MS to detect DUBs labeled with DUB active site inhibitors and was tested to confirm the inhibitory profile of two small molecule inhibitors, PR-619 and P022077. Data presented in the publication confirm the selective inhibition of USP7 in human cells treated with P022077, in contrast to the pan-DUB inhibition profile of the tool compound PR-619 in the same cells.

“Activity-Based Chemical Proteomics Accelerates Inhibitor Development for Deubiquitylating Enzymes”

Senior author Benedikt Kessler noted that the studies were made possible by Progenra's collection of highly selective and non-selective DUB inhibitor tool compounds. Mikael Altun, the lead author, stated that combining DUB active site probes with proteomics affords researchers, for the first time, the ability to generate DUB inhibition profiles and measure changes in the content of the substrates of DUBs in living cells - a key translational step in the development of new drugs for the treatment of cancer, pathogen infection and neurodegenerative disorders.