Fragment-based ligand discovery for the inhibition of protein-protein interactions

Monday 23 February 2015, 1.00PM

Speaker(s): Dr Marko Hyvonen, Dept of Biochemistry, University of Cambridge

Fragment-based ligand discovery (FBLD) is a target-driven approach for the development of chemical tools and lead molecules for drug development. It requires continuous assessment of inhibitor binding using biophysical and structural biology methods from the very first fragment screening and through the process of chemical elaboration of fragment hits to high affinity inhibitors.  We are using FBLD methods to develop inhibitors against protein-protein interactions in DNA repair
and signalling pathways. We have progressed initial fragment hits to nanomolar inhibitors against an interaction between human recombinase, RAD51, and its interacting partner BRCA2 using these approaches. I will describe this process from the early protein work and the development of robust model systems for biophysical assays and crystallography, to characterisation of the binding site with peptidic tools and elaboration of fragment hits to inhibitors with activity in cellular assays.

Location: The Dianna Bowles Lecture Theatre (K018)

Admission: Open

Email: anna.oconnell@york.ac.uk