Project Details
Projekt
Structure-based development of covalent DUB inhibitors for the study and treatment of Chlamydia trachomatis infections
Subject Area
Pharmacy
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 572213419
Chlamydia trachomatis is the most common pathogen for sexually transmitted diseases worldwide. Since this bacterium is reproducing itself obligate intracellularly, its pharmacotherapy is challenging and first resistances have been described. The bacterial deubiquitinase ChlaDUB1 protects the bacterium against intracellular degradation in the host cell. In previous work, we were able to develop the first ChlaDUB1 inhibitors and we could show that this DUB can be inhibited selectively. In cellular studies we could also show for the first time, that ChlaDUB1 inhibition acts antibacterial and therefore opens the way to an entirely new class of antibacterial agents. The compounds obtained so far are only moderately active though and show cytotoxicity at higher concentrations. Therefore, we want to apply structural-biological and computer-assisted methods (molecular docking, molecular dynamics simulations and quantum chemical calculations) to develop highly active and therapeutically applicable compounds, that are selective over human DUBs. We will also use this data to develop molecular tool compounds for obtaining further information about the largely unknown reproduction pathway of chlamydia. This includes click-chemical probe development for microscopic visualization, as well as for studies regarding selectivity and permeability. Furthermore, with the support structure-based and computer-assisted methods based on the results obtained, photopharmacological probes are to be designed and synthesized to enable the study of the role of ChlaDUB1 inhibition with high spatio-temporal resolution. We aim to establish therapeutic applicability of novel ChlaDUB1 inhibitors as well as the development of molecular tool compounds for (anti-)microbial research.
DFG Programme
Research Grants
International Connection
USA
Cooperation Partner
Professor Dr. Martin Conda-Sheridan
Co-Investigator
Professorin Dr. Caroline Kisker
