Drug Discovery

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Drug discovery, which bridges the gap between Chemistry and Biomedical Sciences, has become a major goal of modern science and typifies a discipline in which the successful translation of basic research into novel therapeutic strategies is the key to success. Although target validation and the significance of assay systems still need to be improved, the advent of Genomics, Combinatorial Chemistry and High-Throughput Screening has substantially extended the impact of Drug Discovery. One important aspect of drug research centers on understanding biomolecular structure, function and signaling pathways with the goal of creating new chemical entities. At the other end of the spectrum, challenging synthetic techniques such as diversity oriented synthesis and click chemistry are becoming ever more important in drug research and development. The concept of the chiral switch, which requires that enantiomerically pure drugs be developed, makes modern stereoselective organic synthetic methods essential. In silico techniques, which include bio- and cheminformatics, structure-activity relationships and modelling receptor-ligand interactions, play a crucial role in modern drug research and are better established and accepted in this area than in any other in chemistry. Erlangen possesses internationally recognized expertise from which the Drug Discovery program will benefit. The different participating laboratories cover the major topics and have already established strong working relationships, both in research and teaching. The main module of the life-science branch of the innovative Molecular Science Masters course in Erlangen, Drug Discovery, is, for instance taught jointly by the Chairs of Medicinal Chemistry, Microbiology, Food Chemistry and the Computer-Chemistry-Center. These institutions also make up the “tetracycline triangle”, which uses an interdisciplinary approach to investigate one of today’s most important signal-transduction systems, the tetracycline repressor, within the Cooperative Research Center SFB 473 (Mechanisms of Transcriptional Regulation).
Elucidating macromolecular structures or biological pathways as starting points for the rational development of bioactive agents is termed structure-based drug design. In combination with molecular modeling, fluorescence-based recognition experiments and molecular pharmacology, fundamental molecular understanding of biological activity at the molecular level is used to design highly selective drug candidates. Target-oriented synthesis (TOS) and biological testing can also yield reliable analyses of binding modes and signaling processes provide explanations for subtype selectivity and elucidate the molecular origins of ligand efficacy. With the aim of discovering molecular probes and drug candidates for allosteric target proteins, PeterGmeiner’s group investigates design, chemical synthesis and pharmacological properties of subtype-selective GPCR ligands, TetR effectors (SFB 473) and bioactive agents for the treatment of prion-related diseases. In this context, radioligand binding studies and functional assays reveal the structural origins of subtype selectivity and intrinsic activity. Within these topics, the Gmeiner laboratory contributes to highly attractive developments in CNS-active drugs and gene therapy.