Fundamental Research in Chemical Biology

Chemical biology research at the Leiden Institute of Chemistry is aimed at understanding biological processes at the molecular level to strengthen the knowledge base of human health and disease. The approach to achieve this goal is a fundamental chemical one; with the aid of chemical probes biological systems are interrogated.

This highly generalized description covers a range of chemical probes, both large and small, with which a number of biological systems varying in complexity are studied. Our panel of chemical probes include enzyme inhibitors and receptor ligands and application of these to a biological system, say a tissue culture or animal model (zebrafish), may influence metabolic pathways, leading to altered protein or metabolite levels. A more advanced class of enzyme inhibitors, known as activity-based probes, provide the means to covalently and irreversibly modify and tag their biological targets, which may then be identified and linked to the underlying physiological event, for example through proteomics approaches. Biological targets modified by activity-based probes can include proteins and metabolites. Another class of chemical probes that are central in our chemical biology research are those that can be attached to the desired biomolecule which then can be studied by means of various imaging techniques (biochemical techniques, NMR). Finally, biomolecules themselves or their synthetic mimics will be used in artificial systems designed to emulate biological systems. Supramolecular assemblies and biomaterials are used to manipulate physiological processes, for example to direct cell growth, and to develop new tools for targeted delivery of chemical probes.

The Leiden Chemical Biology research can be distinguished from chemical biology focus areas created at other Dutch Universities both in the nature of the tools and techniques aimed for and in the research objectives. With respect to the tools and techniques, these are designed and prepared through advanced synthetic organic chemistry, and our broad expertise in the design of enzyme inhibitors, activity-based probes, fluorescent labels and spin labels gives our chemical biology research a unique edge within the Netherlands. Our chemical biology research is conducted in the context of health and disease, and aims to acquire knowledge, tools and techniques for human medicine. Enzyme inhibitors or receptor ligands may become lead compounds in drug development whereas activity-based probes may evolve to become diagnostic tools to detect disease states and monitor the efficacy of therapeutic interventions. Next to this our fundamental studies on the interaction of biomolecules may deliver new insights into the molecular background of disease states. Using the different approaches at the molecular level we contribute to the development of new diagnostic tools and therapeutics, resulting in solutions for current disease states.

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