VU University

Dr. Iwan de Esch
De Boelelaan 1085
1081 HV Amsterdam
The Netherlands

Research of the Medicinal Chemistry Section of the VU University Amsterdam focuses on membrane bound receptors, in particular ligand-gated ion channels (LGICs) and G Protein-Coupled Receptors (GPCRs). The section aims to obtain detailed molecular understanding of the mechanisms of action of biologically active molecules. To this end, drug design and synthesis are integrated with pharmacological and biochemical characterization. The section has a special interest in fragment-based drug discovery as an emerging and efficient drug design approach.

In the context of Neurocypres, we will translate the derived structural information (Xray analysis, Sixma – partner 2), biophysical screening data (SPR, Danielson – partner 20; NMR, Spyroulias – partner 15) and pharmacological evaluation (Lummis – partner 5, Smit – partner 2, Sieghart – partner 6, Corringer – partner 7, Bertrand – partner 12) into models that describe ligand-receptor interaction (collaboration with Lummis – partner 5, Spyroulias – partner 15). This will lead to the design of new protein tools (Smit – partner 1, Lummis – partner 5). It will also enable the design and synthesis of novel ligands for CLRs. By integrating both the computational design and the synthetic chemistry efforts, the chemical tractability of novel ligands is ensured. Ideally, series of compounds are synthesized using parallel and high throughput chemistry equipment (e.g. microwaves, carousels, a controlled lab reactor, prep-LCMS and automated parallel flash purification equipment, among others). These facilities ensure sufficient high chemistry output and efficient hit finding and optimization. Next partner >