Our Research Interests
Carbohydrates are involved in numerous biologically important recognition and signaling processes. Examples range from their involvement in protein folding to cell adhesion processes. Our understanding of the underlying mechanisms, however, is just at the beginning and methods for their elucidation need further development. The general aim of our group is to contribute to the elucidation of the biological functions of carbohydrates employing the methods of synthetic organic chemistry in combination with biochemical and cell biological techniques.
One focus of our research is the investigation and application of multivalent carbohydrate-protein interactions. Since individual carbohydrate epitopes are bound by proteins with only low affinity, Nature uses multivalent interactions (i.e., the simultaneous interaction of several ligands of one biological unit (molecule, surface) with several receptors of another unit) to achieve the required high affinity. We study the structure and mechanism of multivalent carbohydrate-protein interactions by a combination of various analytical techniques (X-ray crystallography, EPR spectroscopy, isothermal titration calorimetry, dynamic light scattering, ...) employing synthetic molecules. Furthermore, we exploit the gained insight for the development of artificial multivalent ligands that are able to inhibit natural carbohydrate recognition processes.
Another focus of the group is the development and application of bioorthogonal ligation reactions for the visualization of carbohydrates in living cells. For the incorporation of modified carbohydrate derivatives into cells we use metabolic glycoengineering. Applying the inverse-electron-demand Diels-Alder (IEDDA) reaction, it was possible to detect two and even three carbohydrate derivatives simultaneously in one experiment. Furthermore, we succeeded in the visualization of protein-specific glycosylation within living cells by FLIM-FRET microscopy.
In the area of peptide science, we are interested in the biological roles of microcystins, a group of toxins produced by cyanobacteria (blue-green algae). We developed the first isomerization-free total synthesis of these cyclic heptapeptides. Currently, we carry out structure-activity relationship studies of different synthetic microcystin derivatives and we screen for interaction partners of these bacterial toxins. In addition, the group is involved in the development of new methods for the preparation of glycopeptides and the synthesis of carbohydrate mimics that interact with certain RNA structures.
For further details, please see our list of publications.