is the synthesis of chemical structures which are used as molecular probes in biological test systems. Compounds identified as biologically actives are optimized and the molecular mechanisms of action and structure activity relationships are investigated.
Image of the protein kinase GSK-3 molecule hosting the protein kinase inhibitor alsterpaullone in its ATP binding site. The protein is depicted in the cartoon mode, with helices shown as yellow and beta-sheets shown as blue ribbons, connected by loops depicted as grey tubes.
Protein Kinases
are the main biological targets of our research compounds. These phosphorylating enzymes are involved in manifold biological regulation mechanisms. The inhibition of protein kinases is one of the major strategies in industrial drug development.
Potential therapeutic areas
of our protein kinase inhibitors are for instance
In both diseases a therapeutic benefit might be achieved by inhibiting the excessive growth of cells (either tumor cells or infectious microbes) by protein kinase inhibitors without harming normal cells of the host.
The commercially most successful compounds
from our lab are the paullones. Our molecular entities kenpaullone and alsterpaullone are offered as standard tools for inhibition of cyclin-dependent kinases and of glycogen synthase kinase-3 (GSK-3) by many biochemical vendors. Our 1-azakenpaullone is commercially available as selective GSK-3 inhibitor.
Comparison of alsterpaullone and an ATP analogue positioned in the ATP binding pocket of GSK-3 (X-ray structure of GSK-3/inhibitor complex: J.A.Bertrand et al., J. Mol. Biol. 2003, 333, (393-407)
National and International Cooperations
are an indispensable prerequisite of our research projects. Our work was funded by national and international organizations and foundations (European Commission, Deutsche Forschungsgemeinschaft, State of Lower Saxonia (Niedersächsisches Vorab), Bundesministerium für Bildung und Forschung, National Cancer Institute, Mukoviszidose e.V., etc.)