CHEMICAL SYNTHESIS OF SMALL MOLECULES TO MODULATE PROTEIN-PROTEIN INTERACTIONS AND PROTEIN RELOCALIZATION EVENTS.
Small molecules that compete with native protein-protein interaction interfaces offer new options to modulate functional protein networks (including protein localization). This project aims at the design and chemical synthesis of small molecules, which selectively influence the cellular localization of certain proteins by competing with their natural (protein) binding partners. As the core competence of the group lies in the field of synthetic organic chemistry, the project requires intense cooperation with groups from the biological sciences (structural biology, protein biochemistry, cellular assays, etc.), thus providing a truly interdisciplinary project.
Chiha, S., A. Soicke, M. Barone, M. Muller, J. Bruns, R. Opitz, J.M. Neudorfl, R. Kuhne, and H.G. Schmalz (2018), Design and Synthesis of Building Blocks for PPII-Helix Secondary-Structure Mimetics: A Stereoselective Entry to 4-Substituted 5-Vinylprolines (vol 2018, pg 455, 2018). European Journal of Organic Chemistry (46): p. 6597-6597.
Opitz, R., M. Muller, C. Reuter, M. Barone, A. Soicke, Y. Roske, K. Piotukh, P. Huy, M. Beerbaum, B. Wiesner, M. Beyermann, P. Schmieder, C. Freund, R. Volkmer, H. Oschkinat, H.G. Schmalz, and R. Kuhne (2015), A modular toolkit to inhibit proline-rich motif-mediated protein-protein interactions. Proceedings of the National Academy of Sciences of the United States of America. 112(16): p. 5011-5016.
Reuter, C., R. Opitz, A. Soicke, S. Dohmen, M. Barone, S. Chiha, M.T. Klein, J.M. Neudorfl, R. Kuhne, and H.G. Schmalz (2015), Design and Stereoselective Synthesis of ProM-2: A Spirocyclic Diproline Mimetic with Polyproline Type II (PPII) Helix Conformation. Chemistry-a European Journal. 21(23): p. 8464-8470.