Research areas

Our research focuses on the development of molecular tools and drug candidates for G protein-coupled receptors (GPCRs). These receptors play an important role in the transmission of signals across the cell membrane and are involved in various physiological processes, including light, smell, and taste sensing. However, GPCR-mediated signaling can also contribute to the development of diseases. Thus, GPCRs are of outstanding importance as target structures for drug discovery. A special focus of our GPCR-based research is on a recently identified intracellular allosteric binding site (IABS) that can be targeted with small molecule antagonists. This IABS has mainly been observed at GPCRs of the chemokine receptor subfamily (e. g. CCR9). Targeting these allosteric binding sites opens up new approaches in terms of controlling receptor selectivity, functional selectivity (biased signaling) and enables the use of innovative intracellular drug targeting strategies.

Image taken from Huber et al. Angew. Chem. Int. Ed. 2022, 61, e202116782.

Furthermore, we work on the structure-based development of enzyme inhibitors. Our interest focuses on both human enzymes (e.g. the histone deacetylases HDAC6 and Sirt2) and enzymes of human pathogens (e.g. Pseudomonas aeruginosa, Trypanosoma cruzi).

Image taken from Sinatra et al. ChemRxiv, 2023, DOI: 10.26434/chemrxiv-2023-dpx9n-v2.

Application for the drug candidates and molecular tools developed in our working group are in the treatment of inflammatory diseases, cancer, and infections.