Research Training Group “Medicinal Chemistry of Selective GPCR Ligands” (GRK 1910)

Topic and Aims of the Research Training Group

Approximately 30 % of the drugs on the market exert their biological activities upon binding to G-protein coupled receptors (GPCRs). As biological targets, GPCRs are associated with exceptional progress in the field of drug research, enabling the application of molecular strategies for the discovery of innovative therapeutic principles. Severe diseases are frequently associated with dysfunctions of GPCRs. The biological activity of GPCR agonists and antagonists is determined by multidimensional selectivity profiles, resulting in both desired and adverse effects. Besides receptor subtype selectivity, this includes functional selectivity (biased signaling), selectivity for receptor conformations, receptor dimers, allosteric receptor sites, orthologs and mutants.

The proposed Research Training Group aims to explore the ligand induced control of monoaminergic and peptidergic GPCRs at aforementioned levels of selectivity. In addition to the elucidation of molecular mechanisms, we attempt to contribute to a rational development of functionally selective GPCR drugs for the treatment of chronic inflammatory, cardiovascular and CNS diseases and for diagnostic purposes. The research programme is strongly interdisciplinary, covering computer assisted design of selective ligands and molecular tools with the aid of GPCR models, chemical synthesis of target compounds, novel concepts of bioisosteric replacement, the investigation of ligand-receptor interactions and the elaboration of functional selectivity by analysis of ligand-specific signaling including the development of appropriate assays.

The programme specific interdisciplinary qualification profile integrates chemical, radiopharmaceutical, pharmacological, molecular biological, bioanalytical and biochemical aspects of drug research as well as methods of modern drug discovery. The main issues of the qualification programmes for graduates and postdoctoral associates in the Research Training Group are retreats, workshops and seminar/webinar days, dealing with and promoting the core research idea. Furthermore, within their projects all graduates will get the opportunity to work for 3-4 months in the research labora-tory of a collaborator abroad to acquire new knowledge, apply modern methods and techniques and to gain international experience even before the completion of the doctorate.