About the Research Group
We apply novel chemistry within a biology setting to enhance understanding of diseases on the molecular level and to develop new or personalized drugs. Our targets of interest are studies on nuclear receptors that play a role in cancers and on the visualization and assembly processes of proteins, such as disease relevant membrane proteins.
Our group synthesizes novel molecules and supramolecular architectures and explores these for understanding and modulating protein-protein interactions.
- The nuclear receptor – cofactor interaction is the key protein protein interaction that transfers ligand induced changes in the nuclear receptor conformation to the transcriptional machinery. A molecular understanding of this process and its regulation is necessary to fully control and predict the effects of nuclear receptor targeting. Using several Nuclear Receptors as working horses (including ER, RXR, and ROR), molecular strategies to elucidate this protein-protein interaction at the molecular level are developed.
- 14-3-3 proteins are scaffold proteins acting to regulate the function and localization of their binding partners. Our group develops drug discovery strategies to stabilize or inhibit 14-3-3 based protein-protein interactions and thus contributes to novel therapeutic concepts for the diseases in which 14-3-3 proteins play a role. Notably, the complex interplay of the multiple phosphorylated protein binding partners, the bivalent 14-3-3 platform and small molecules constitutes an attractive multivalent complex system.
- Supramolecular chemistry has primarily found its inspiration in biomolecules and their interactions. Synthetic host-guest systems are applied for the controlled and reversible dimerization and immobilization of proteins. Specifically, cucurbituril based systems are being used to recognize specific protein elements. In this way, supramolecular inducers of dimerization can be generated that act as allosteric modulators and activators of enzyme dimerization and activation. Supramolecular self-assembling platforms are synthesized to enable 1-D protein assembly along a self-assembling scaffold.
These three lines of research are combined to generate synthetic supramolecular signaling systems which we use to understand signal transduction and to complement the cell with novel signaling elements.