Universiteit Leiden

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Bio-organic Synthesis

Research

Research at the BIOSYN group is comprised of the following research themes:

Physiological processes in glycobiology and immunology (Prof. dr. Herman Overkleeft)

Irreversible, or mechanism-based, inhibitors are attractive tools in chemical biology. Attachment of a reporter entity, which can be a biotin, a fluorophore, a bioorthogonal tag, a radiolabel or a combination of these, allows for the identification, visualization, identification and spatiotemporal study of the modified enzyme(s) using various techniques and in complex biological systems ranging from cell extracts, living tissue to animal models. This is the field of activity-based protein profiling (ABPP).

Within the group we develop activity-based probes (ABPs) for proteases, glycosidases and a range of other hydrolases and apply these in immunological and glycobiological studies related to health and disease. Together with these ABPs we develop focused libraries of (competitive) inhibitors. Together, this toolset allows us to perform a number of conceptual experiments. In comparative ABPP ABPs are used to discover new enzyme activities and to compare enzyme expression levels in different tissue. In competitive ABPP the focused inhibitor libraries are included to study efficacy and selectivity of these in complex biological samples. In fluorescence polarization ABPP we develop assays amenable for high-throughput screening to discover new chemical entities for inhibiting one of our target enzymes.

Synthetic carbohydrate chemistry for glycobiology (Dr. Jeroen Codée)

Carbohydrates are the most diverse and complex class of biomolecules from both a structural and biological activity point of view. Our research focuses on the development of synthetic tools and strategies, including automated solid phase procedures, to efficiently assemble well-defined oligosaccharides and glycoconjugates to unravel their mode of action at the molecular level. State-of-the-art synthetic chemistry is used to generate synthetic vaccine modalities (directed at bacterial infections and cancer) and in the design and synthesis of inhibitors and probes to study carbohydrate metabolism.

On the interface between chemistry and immunology (Dr. Sander van Kasteren)

The research of my group focuses on developing new chemical tricks to study and manipulate the immune system. We are particularly interested in the field of therapeutic cancer vaccination: where we try to harness a patient's own immune system to fight off an existing tumour. To achieve this, we make new compounds and test these in model vaccines. We also study the biochemical changes our compounds induce in great detail. The techniques we use are a combination of organic synthesis, cell biology and immunology.

Synthetic biopolymer conjugates (Prof. dr. Gijs van der Marel)

Nucleic acids, peptides and carbohydrates are biopolymers that play essential roles in a wide array of biological processes. The same holds for naturally occurring conjugates of these molecules. To elucidate the mechanism of action of these molecules at a molecular level and ultimately modulate the biological processes in which they are involved, our group is focused on the development of synthetic approaches to (modified) oligomers and corresponding conjugates of these biopolymers. The development of new glycosylation procedures, phosphorylation methods, conjugation techniques and protective group manipulations are examples of synthetic approaches that are elaborated to attain structurally well-defined target molecules. The biological evaluation is carried out in collaboration with international renowned research groups.