Fragment-Based Drug Design
J.-F. Guichou, M. Gelin, G. Labesse, M. Schneider
The group is developing fragment-based drug design using X-ray crystallography, biophysics, chemo-informatics and soft/bio-compatible chemistry for therapeutics applications in virology,
oncology and infectious diseases.
Designing new drugs remains highly challenging and complex with potential failure at each step. The group is developing an integrated approach for quicker and more rational design of drugs. Based on our expertise in ligand screening by X-ray crystallography, we have established a fully robotized platform for crystallization, crystal growth survey and diffraction in 96-well plates. This set-up is being used for the screening of fragment or more elaborate compounds generate by soft and/or bio-compatible chemistry. The group had also developed a fully automatic treatment for the resolution of the complex small molecule-protein (~150 structures per months). Combining all the structural information and the biophysics characterization (TSA, ITC, ...), the group design new therapeutic compounds which are tested through collaborations for their biological effects.
Main Collaborators : S. Pochet (I. Pasteur). I. Krimm (CNRS), JM. Pawlotsky (Hôpital Henri-Mondor). S. Roche (CNRS), P. Santa Barbara (INSERM), M. McGee (Dublin).
References : Gelin et al., Structure, 2012. Gelin et al., Acta Cryst D, 2015. Sagnol et al., NAR, 2015. Ahmed-Belkacem et al., Nat. Comm., 2016.