Posted on 14 July 2015
In the last ten years, Fragment-Based Lead Discovery (FBLD, also known as Fragment-Based Drug Discovery FBDD) has proven to be an effective approach towards the discovery of small molecule compounds (ligands) that can bind to biological target molecules. The key feature of this approach is that ligand discovery begins with the screening of low molecular weight compounds (fragments) that have a higher chance of binding to a target in comparison to whole (drug) candidate molecules. This means that small libraries of around 1500 fragments are sufficient for finding hits against most targets. Such hits can then be grown or merged to provide lead compounds. Overall, this means a much smaller investment is required in terms of automation and development of compounds in comparison to those required by High Throughput Screening (HTS), thereby enabling small companies and academic groups to participate in the drug hunting efforts. More recently, fragment-based approaches are also used to interrogate biological systems, helping to unravel cellular processes and identify new drug targets.
Three PhD students will be based in York exploring synthesis of fragments with novel shapes, developing fragment methods to improve industrial enzymes and using fragments to identify new ways to develop antibiotics. In addition, other students from the cohort of 15 will spend some of their time in York on placements. This project builds on the investment in structural and chemical biology at York, most recently through the C2D2 infrastructure funding provided by the Wellcome Trust.
Academic beneficiary partners: Iwan de Esch (Coordinator, VU University Amsterdam, NL), Rod Hubbard (University of York, UK), Georgy Keseru (Hungarian Academy of Sciences, HU), Xavier Barril (Universitat de Barcelona, SP).
Industrial beneficiary partners: Ben Davis (Vernalis, UK), Gregg Siegal (Zobio, NL), Helena Danielson (Beactica, SE), Wolfgang Jahnke (Novartis, CH).
Partner organizations: GSK (UK), Roche (CH), Servier (FR), IOTA (UK) and 24 Media Labs (NL).