Design, Synthesis and Study of Enzyme Inhibitors, Nucleoside & Nucleotide Analogues and Prodrugs; Design of Molecular Probes; Design of Organic Semiconductors; Study of Anticancer and Antiviral Drug Action and Resistance.
Our laboratory was engaged in a multidisciplinary anticancer and antiviral drug discovery research endeavor that utilized a combination of mechanism-based and structure-based design strategies. Our drug discovery effort focused on the design of mechanism-based inhibitors of key enzymes in nucleotide metabolism, responsible for the biosynthesis of the building blocks of DNA and RNA. These design strategies required considerable insight into the molecular mechanisms of catalysis performed by the target enzymes, which are probed by kinetic and equilibrium isotope effect studies, and molecular modeling. Enzyme inhibitory activities of the compounds synthesized are determined using purified enzymes, as well as cellular enzyme systems.