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.
