Research topics

Rational design of multi-target drugs

Dual or multi-target ligands have several advantages compared with selective compounds, including improved efficacy and more simple pharmacokinetic and pharmacodynamic properties in comparison to the combination of several drugs. Unfortunately, the rational design of polypharmacological compounds is a rather hard task and not well established. We use two different strategies for this task. On the one hand, we chemically link two known pharmacophores in order to obtain dual inhibitors. On the other hand, we are developing computer-aided methods which allow to combine the pharmacophores of different targets in one chemical compound.

Fragment-based drug design

Fragment based approaches rely on search of molecular fragments (chemical compounds with a molecular weight<300) which can be extended or linked in order to obtain potent drug-like molecules. We combine computer-aided design methods with saturation-transfer-difference (STD)-NMR and biochemical assays for retrieval of fragments with desired biochemical activity. Furthermore, we extend this approach to fragment-based design of multi-target drugs.

Design of lipid signaling modulators

Lipid mediators play an important role in different pathological processes including inflammation, cardiovascular diseases, cancer and many more. We design chemical compounds which interfere with different lipid signaling pathways and which can be potentially used as drugs or pharmacological tools.



VAMMPIRE: a matched molecular pairs database for structure based drug design and optimization

Structure-based optimization to improve the affinity of a lead compound is an established approach in drug discovery. Knowledge-based databases holding molecular replacements can be supportive in the optimization process. We introduce a strategy to relate the substitution effect within Matched Molecular Pairs (MMPs) to the atom environment within the co-crystallized protein-ligand complex. VAMMPIRE (Virtually Aligned Matched Molecular Pairs Including Receptor Environment) database and the supplementary web interface provide valuable information for structure-based lead optimization.

Weber, J., Achenbach, J., Moser, D., Proschak, E., Spänkuch, B.
VAMMPIRE-LORD: a web server for straightforward lead optimization using matched molecular pairs. J. Chem Inf. Model. 55; 207-213