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Our latest research featured in JACS.

Covalent probes can display unmatched potency, selectivity and duration of action; however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversible fragment screening, but such electrophilic fragments were considered non-selective and were rarely screened. We hypothesized that mild electrophiles might overcome the selectivity challenge and constructed a library of 993 mildly electrophilic fragments. We characterized this library by a new high-throughput thiol-reactivity assay and screened them against ten cysteine-containing proteins. Highly reactive and promiscuous fragments were rare and could be easily eliminated. By contrast, we found hits for most targets. Combining our approach with high-throughput crystallography allowed rapid progression to potent and selective probes for two enzymes, the deubiquitinase OTUB2 and the pyrophosphatase NUDT7. No inhibitors were previously known for either. This study highlights the potential of electrophile-fragment screening as a practical and efficient tool for covalent-ligand discovery.

Through a partnership between Novo Nordisk and the University of Oxford, we are now seeking highly motivated individuals to join our lab as postdoctoral research fellows. We have two 3-year fellowships available:

Click here for further details including how to apply

A collaborative partnership between the Huber Lab, Myeloma UK and the Joyce and Norman Freed Foundation support our research efforts in improving treatment and finding a cure for multiple myeloma. The Freed Foundation recently met with our research team at the Structural Genomics Consortium to hear about the project and its latest progress.

Alison Goldberg said: “Having supported Myeloma UK over many years, my sister Sara and I have been impressed with the impact Myeloma UK and its work has had on myeloma patients.  We wanted to visit the SGC and to understand the role they play.  We were so impressed with the facilities at the SGC as well as the excellent progress being made with the research.  Results from this study will help to optimise the use of current and future treatments. It’s really encouraging to see the impact our funding is having on research.”

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