At the MRC-PPU we have developed a novel high-throughput MALDI-TOF mass spectrometry based method for screening for DUBs inhibitors using unmodified diubiquitin isomer substrates. The method has been published in 2014 in Nature Communications: “Screening of DUB activity and specificity by MALDI-TOF mass spectrometry”, Ritorto MS et al. Further detail can be found in the paper "High-throughput matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry-based deubiquitylating enzyme assay for drug discovery" by De Cesare et al in Nature Protocols 2020.
Based on this approach, we offer a high throughput MALDI-TOF based drug discovery platform for the identification and characterisation of lead compounds active against specific DUBs. We offer the screening of large library compounds at a single concentration (DUBs inhibitor screening) against one single DUB as a first step for lead compounds identification. These can be further characterised for their target-specificity by testing them against a panel of 51 DUBs currently available in our unit (DUBs Profiling). Finally, we can determine the compounds potency through calculation of their IC50.
Our facility is managed as an independent entity (within the MRC Protein Phosphorylation and Ubiquitylation Unit). Our staff are trained to ensure that strict confidentiality is maintained with regard to the nature of each customer’s project and samples. Only facility staff have access to customer details and sample information/results files and this information is never made available to others. You can rest assured that your confidentiality will always be respected in every aspect of our interaction with you.
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