Partner 13

Short name: TUBS

Principal Investigator: Prof. Conrad Kunick, Technische Universität Braunschweig (TUBS)

Host Institution: The Technische Universität Carolo-Wilhelmina zu Braunschweig is a research-oriented university with a focus in engineering and life sciences hosting 14,000 students in more than 100 scientific institutions. The Institute of Pharmaceutical Chemistry is one of four institutes in the University Center of Pharmaceutical Sciences. Within the institute, three research groups headed by professors are pursuing scientific projects in the fields of Medicinal Chemistry, Chemometrics and Pharmaceutical Analysis. The department facilities are fully equipped with laboratories for synthetic and analytical organic chemistry. Instruments available for the tasks within the consortium comprise a parallel reactor station, a computer-operated microwave reactor, DAD-HPLC, FT-IR, a fluorimetry instrument, a UV/VIS-spectrometry device, and a C,H,N-elemental analyzer. HPLC/MS, NMR, HRMS and x-ray structure analysis are available in the Center of Pharmaceutical Sciences and in the analytical unit of the chemistry department.

Prof. Conrad Kunick is the head of laboratory in the Institute of Pharmaceutical Chemistry at the Technische Universität Carolo-Wilhelmina in Braunschweig (TUBS). His research group has a broad experience in the design and development of biologically active structures, namely kinase inhibitors and antiproliferative compounds. The paullones, a class of kinase inhibitors developed in collaboration by the Kunick group and the group of Laurent Meijer (partner 10), have been commercialized and are used worldwide as biochemical tools in cell biology, molecular pharmacology and drug discovery. Current drug development projects are directed to new therapeutics against cancer (in cooperation with KTB Tumorforschungs GmbH, Freiburg, Germany, and the National Cancer Institute, Bethesda, USA), diabetes (in cooperation with Develogen AG, Göttingen, Germany), and tropical diseases (in cooperation with the CNRS Station Biologique, Roscoff, France). The group is also participating in an Integrated Project (IP) within the 6^th European framework program (LSHB-CT-2004-503467 PRO-KINASERESEARCH; “Protein kinases – Novel Drug Targets of Post Genomic Era”). In the setting of this IP the group has recently developed and filed a new chemotype against leishmaniasis. Earlier projects were funded by the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), and the National Cancer Institute (NCI). Other key personnel: Dr. L. Preu (permanently employed by TUBS, scientist, lecturer, expert in molecular modeling, development of synthesis strategies, two-dimensional NMR and HPLC), M. Söchtig (technician with chemistry background, permanently employed by TUBS, will support all procedures concerning synthesis, logistics and apparatus maintenance) PhD students (to be hired within the project; chemists or pharmacists with good knowledge and skills in Medicinal Chemistry; will be involved in all aspects concerning the synthesis and chemical analysis of new compounds).

Selected Publications:

1. Reichwald, C., Shimony, O., Dunkel, U., Sacerdoti-Sierra, N., Jaffe, C. L., and Kunick C., 2-(3-Aryl-3-oxopropen-1-yl)-9-tert-butyl-paullones: A new antileishmanial chemotype. J. Med. Chem. 2008, 51, 659-665.

2. Reichwald, C., Shimony, O., Sacerdoti-Sierra, N., Jaffe, C. L., and Kunick C., A new Heck reaction modification using ketone Mannich bases as enone precursors: Parallel synthesis of anti-leishmanial chalcones. Bioorg. Med. Chem. Lett. 2008, 18, 1985-1989.
3. Stukenbrock, H., Mußmann, R., Geese, M., Ferandin, Y., Lozach, O., Lemcke, T., Kegel, S., Lomow, A., Burk, U., Dohrmann, C., Meijer, L., Austen, M., and Kunick, C., 9-Cyano-1-azapaullone (cazpaullone), a GSK-3 inhibitor activating pancreatic beta cell protection and replication. J. Med. Chem. 2008, 51, 2196-2207.
4. Prühs C., Kunick C. Darpones and water-soluble aminobutoxylated darpone derivatives are distinguished by matrix COMPARE analysis. Bioorg. Med. Chem. Lett. 2007, 17, 1850-1854.
5. Kunick C., Zeng Z., Gussio R., Zaharevitz D., Leost M., Totzke F., Schächtele C., Kubbutat M. H. G., Meijer L., Lemcke T. Structure-aided optimization of kinase inhibitors derived from alsterpaullone. ChemBioChem 2005, 6, 541-549.