Fragment-based hit discovery for the epigenetic target, BRD3
Earlier this year Peak Protein’s first synchrotron trip took place to collect X-ray data on the target bromodomain 3 (BRD3) in a joint project run together with Sygnature Discovery. BRD3 was chosen as a target in order to test the effectiveness of Sygnature’s recently developed fragment library. While Peak Proteins carried out all the protein production and crystallography, Sygnature’s scientists were responsible for screening the fragments by SPR and ensuring selective binding to the protein. Refining the selection of hits obtained by affinity and solubility enabled us to maximise the probabilities of successfully obtaining fragment bound crystal structures in this initial experiment.
The selected hit compou
nds were either soaked into apo-BRD3 crystals or incorporated using co-crystallisation methods. X-ray data was then collected in beam line I03 at Diamond Light Source in Oxfordshire.
Further details on the background to the project and the approach taken can be found here: BRD3 case study summary Sept 2016
