Structure-based design of synthetic retinoid derivatives with enhance biological activity.

The aim of this project is to define the molecular basis of how various synthetic retinoids elicit specific biological responses. The insight gained from our detailed structural studies combined with biophysical characterization of protein-ligand interaction and cell biological assays will be used to design new ligands with superior chemical and biological properties. The project builds on recent work synthesizing novel retinoid derivatives (Professor AR Whiting), and their subsequent structural and biological characterization (Professor AR Whiting and Dr. E Pohl) that identified how subtle chemical differences lead to significant changes in binding affinities to the different types of protein targets. In order to unravel the molecular basis of these differences we will combine three main strategies, (i) Biophysical experiments including surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC), (ii) molecular modeling studies (iii) synthesis of new compounds.
High Force Research will be involved in the design and planning of all steps in the project, which is part of a wider collaboration between Durham University, led by Professor Whiting and Dr R Valentine (HFR) who also acts as the co-supervisor.