We create and study selective interactions between proteins and small synthetic molecules. Our research projects are interdisciplinary. We apply chemical and physical tools to address questions of biological and medicinal relevance, involving a broad spectrum of techniques ranging from organic chemistry to structural biology. Current research projects include:
Drug discovery technologies
The generation of new drug candidates requires the identification and optimisation of compounds that bind specifically to drug targets. This process is usually conducted in a multi-step linear manner. Our research aims to short-circuit the generation of such compounds by developing novel screening methods that simultaneously report the compound binding event, site and orientation on the target. We capitalise on state-of-the-art biophysical methods (e.g. paramagnetic NMR spectroscopy) and screening platforms (e.g. fragment-based drug discovery).
Development of antiviral agents
Selective therapeutic agents are needed to combat epidemic outbreaks of neglected tropical diseases caused by viruses such as Chikungunya, dengue and Zika. Our research targets viral proteases as the Achilles heel of viral replication. We design selective probes and inhibitors that help to characterise and validate proteases as antiviral drug targets and develop lead compounds for drug discovery campaigns.
Chemical ligation reactions that do not interfere with biological systems are essential to tag and probe proteins. Modern genetic engineering enables the site-specific incorporation of over 100 different unnatural amino acids. We introduce new unnatural amino acids that allow for orthogonal bioconjugation and selective protein tagging. We are also interested in reversible protein modification using the unique binding characteristics of underexplored chemical elements.