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Activity-based protein profiling reveals targets of a cyanopyrrolidine probe

by Dr Ravi Singh

CNPyr mechanism

Congratulations to former PhD student Dr Nattawadee Panyain for publishing in RSC Medicinal Chemistry

UCHL1 is a deubiquitinating (DUB) enzyme that is involved in various cancers, and liver and lung fibrosis. This enzyme is therefore of interest as a potential drug target, however the functions and substrates of UCHL1 are poorly understood.

In this , the authors characterize covalent inhibitors of UCHL1 and use chemical proteomics to generate a comprehensive quantitative profile for on- and off-targets at endogenous cellular abundance. The findings showed that molecules were selective for UCHL1, over other DUBs, but also engaged a range of other targets. These were displayed with good selectivity over the wider proteome, including aldehyde dehydrogenases, redox-sensitive Parkinson's disease related protein PARK7, and glutamine amidotransferase.

We would like to thank , the Royal Thai Government, the , and the for their generous funding.

Congratulations to all involved!

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Reporter

Dr Ravi Singh

Department of Chemistry