№ 399/2014 from Nov 18, 2014
Scientists working in Jörg Rademann's Medicinal Chemistry Group have gained new insights into so-called pockets of proteins. Rademann is a professor of Pharmaceutical and Medicinal Chemistry at both Freie Universität Berlin and the University of Leipzig. The recesses and trenches on the surface of protein molecules are responsible for their correct functioning. Drugs function by binding to these cracks and crevices, thereby turning off disease-relevant protein molecules. The new findings help to better understand the mechanisms of action of already existing drugs, for example, to prevent heart attacks. The scientists are working to explore protein pockets that have not yet been investigated using the new method and thereby develop innovative drugs. The findings were published in the November issue of the journal Nature Communications.
Proteins are molecular machines that control every function of the body as well as each individual cell. The binding of active substances to the pockets of proteins is thus of great importance for the pharmaceutical treatment of diseases: the tighter the protein-binding molecules are attached to the pockets, the firmer is the bond – and the more efficient the drug.
The protein-binding molecules can be identified as they cause a chemical reaction on the surface of proteins, where an enzymatic reaction is started. The dye is split, and there is an increase in fluorescence. "We are able to kill two birds with one stone," says Jörg Rademann. "With the fluorescence, we are able to filter out of thousands of molecules those that are stored in a particular protein pocket. That way we can gain valuable information about the reactivity of the protein surface, and this information can also be used for the development of new drug molecules."
Prof. Dr. Jörg Rademann, Institute of Pharmacy, Freie Universität Berlin, Tel.: +49 30 838-53272, Email: email@example.com
Burda, E. & Rademann, J. Catalytic activation of pre-substrates via dynamic fragment assembly on protein templates. Nature Communications doi:10.1038/ncomms6170 (2014).