The ovarian tumour protease (OTU) family of deubiquitinating enzymes (DUBs) are biochemically well-characterised and of therapeutic interest, however, only a few tool compounds exist to study their cellular function and therapeutic potential. Here, the authors present a chemoproteomics fragment screening platform for identifying DUB-specific hit matter, which combines activity-based protein profiling with high-throughput optimisation to enable rapid elaboration of initial fragment hits against OTU DUBs, and identify an enantioselective chloroacetamide-based covalent fragment for OTUD7B.
- Aini Vuorinen
- Cassandra R. Kennedy
- Katrin Rittinger
