GRK 1910:  Medicinal Chemistry of Selective GPCR Ligands

• Subject Area: Medicine
• Term: from 2013 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 222125149

Approximately 30 % of the approved drugs act via binding to G-protein coupled receptors (GPCRs). As biological targets enabling molecular approaches to the discovery of innovative therapeutic principles, GPCRs are associated with outstanding progress in the field of drug research. Dysfunctions of GPCRs often contribute to the etiology of severe diseases. The biological activity of GPCR agonists and antagonists is based on multidimensional selectivity profiles, resulting in both desired and adverse effects. Such selectivity profiles involve receptor subtype selectivity, functional selectivity (biased signaling) as well as selectivity for receptor conformations, receptor dimers, allosteric receptor sites, orthologs and mutants. In the proposed second grant period, the Research Training Group aims to further investigate the ligand induced control of monoaminergic and peptidergic GPCRs at different levels of selectivity. In addition to the exploration of molecular mechanisms, contributions to rational development of functionally selective GPCR drugs for the treatment of pain, chronic inflammatory, cardiovascular and CNS diseases and for diagnostic purposes are planned. The research program remains as highly interdisciplinary as before, covering computer assisted design of selective ligands and molecular tools with the aid of GPCR models, chemical syntheses of target compounds, novel approaches of bioisosteric replacement, the investigation of ligand-receptor interactions and the identification and verification of functional selectivity by analysis of ligand-specific signaling including the development of appropriate assays. The interdisciplinary qualification profile integrates chemical, radiopharmaceutical, pharmacological, molecular biological, bioanalytical and biochemical aspects of drug research as well as methods of modern drug design. The qualification programme for graduates and postdoctoral associates in the Research Training Group mainly consists of retreats, workshops and seminars, dealing with and promoting the core research idea. Furthermore, within their projects all graduates get the opportunity to work for 3-4 months in the research laboratory of a foreign collaborator to acquire new skills, apply modern methods and techniques and to gain international experience.

• DFG Programme: Research Training Groups
• Applicant Institution: Friedrich-Alexander-Universität Erlangen-Nürnberg
• Co-Applicant Institution: Universität Regensburg
• Spokesperson: Professor Dr. Peter Gmeiner
• Participating Researchers: Professor Dr. Armin Buschauer (†); Professor Dr. Timothy Clark; Professorin Dr. Jutta Eichler; Professorin Dr. Kristina Friedland; Professor Dr. Markus Heinrich; Professor Dr. Max Keller; Professor Dr. Burkhard König; Professorin Dr. Monika Pischetsrieder; Professor Dr. Olaf Prante; Professor Dr. Oliver Reiser; Professor Dr. Heinrich Sticht; Privatdozentin Dr. Andrea Strasser; Professor Dr. Joachim Wegener; Dr. Dorothée Weikert, since 1/2017