+44 1223 790975
Scientific Tracks Abstracts: Drug Design
Protein methyltransferases (PMTs) are a novel gene class of medical relevance involved in epigenetic and other biological mechanisms, that transfer a methyl group from the cofactor S-adenosylmethionine to specific lysine or arginine residues of substrate proteins. Both cofactor and substrate binding pockets are druggable, and potent inhibitors have recently reported that bind at either site. Systematic analysis of available structures provides important insight for drug design. We will show how limited chemical variations on the cofactor scaffold can induce dramatic changes in potency and selectivity. We will also propose a strategy for the development of chemical libraries where a limited number of warheads, each occupying the lysine-channel of multiple enzymes, would be decorated by different substituents.
Matthieu Schapira holds a Ph.D in biochemistry from Ecole Normale Superieure, Paris. After graduating in 1995, he completed a couple post-docs in protein crystallography and computational chemistry at New York University Medical Center. In 2000, he joined Molsoft, a San-Diego based biotech, as senior research scientist. In 2003, he moved to Lyon, France, to lead structure-based drug design at Aptanomics/Imaxio, a drug discovery start- up. In 2007, he joined the Structural Genomics Consortium in Toronto as head of research informatics. Matthieu holds adjunct Associate Professor cross-appointments with the Departments of Pharmacology at University of Toronto, and at New York University.