Organic Chemistry Seminar: Chemical Space Discovery of Bioactive Small Molecules and Peptides
Prof. Jean-Louis Reymond, University of Berne, Switzerland
Abstract:
Chemical space describes the ensemble of all molecules that are possible by assembling atoms through covalent bonds. This concept is particularly relevant in drug discovery, where new molecular entities are constantly needed to develop new drugs addressing unmet medical needs. In our research we design cheminformatics methods for enumerating, mapping and virtual screening the chemical space of small organic molecules and peptides.1, 2 We then implement these methods to choose, synthesize and test molecules in the laboratory. I will describe applications targeting ion channels,3 transporters4 and enzymes,5 as well as new peptide based antibiotics against multi-drug resistant bacteria.6
References:
-
Reymond, J. L. The Chemical Space Project. Acc. Chem. Res. 2015, 48, 722-730.
-
Jin, X.; Awale, M.; Zasso, M.; Kostro, D.; Patiny, L.; Reymond, J. L. Pdb-Explorer: A Web-Based Interactive Map of the Protein Data Bank in Shape Space. BMC Bioinformatics 2015, 16, 339.
-
Simonin, C.; Awale, M.; Brand, M.; van Deursen, R.; Schwartz, J.; Fine, M.; Kovacs, G.; Häfliger, P.; Gyimesi, G.; Sithampari, A.; Charles, R. P.; Hediger, M.; Reymond, J. L. Optimization of Trpv6 Calcium Channel Inhibitors Using a New 3d Ligand Based Virtual Screening Method. Angew. Chem., Int. Ed. Engl. 2015, 54, 14748-14752.
-
Montalbetti, N.; Simonin, A.; Simonin, C.; Awale, M.; Reymond, J. L.; Hediger, M. A. Discovery and Characterization of a Novel Non-Competitive Inhibitor of the Divalent Metal Transporter Dmt1/Slc11a2. Biochem. Pharmacol. 2015, 96, 216-224.
-
Kilchmann, F.; Marcaida, M. J.; Kotak, S.; Schick, T.; Boss, S. D.; Awale, M.; Gonczy, P.; Reymond, J. L. Discovery of a Selective Aurora a Kinase Inhibitor by Virtual Screening. J. Med. Chem. 2016, 59, 7188-7211.
-
Pires, J.; Siriwardena, T. N.; Stach, M.; Tinguely, R.; Kasraian, S.; Luzzaro, F.; Leib, S. L.; Darbre, T.; Reymond, J. L.; Endimiani, A. In Vitro Activity of the Novel Antimicrobial Peptide Dendrimer G3kl against Multidrug-Resistant Acinetobacter Baumannii and Pseudomonas Aeruginosa. Antimicrob. Agents Chemother. 2015, 59, 7915-7918.
Seminar Organizer: Dr. Roman Dobrovetsky
