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Organic chemistry of nucleosides and nucleotides with applications in biochemistry and in anticancer and antiviral medicine. Research involving stereochemically defined transformations of nucleic acid components, invention of mechanism-based inhibitors of enzymes vital to cancer cell and/or virus proliferation, and collaborative biochemical evaluation. Primary research is centered on intuitive a priori design and synthesis of nucleoside analogues constructed with features that are chemically activated in the initial steps of an enzyme mechanism where spontaneous subsequent reactions cause enzyme inactivation. The targeted enzymes include S-adenosylhomocysteine and S-ribosylhomocysteine (LuxS) hydrolases and ribonucleotide reductases. Investigation focuses on application of new fluorination methodologies for synthesis of fluoro modified nucleoside analogues. Dr. Wnuk's research group also is interested in the design and synthesis of 18F labeled nucleosides for Positron Emission Imaging. Another area of research concentrates on developing new procedures for radical-mediated cleavage of carbon-sulfur bond in sulfones and application of the vinyl silanes and germanes in Pd-catalyzed cross-coupling reactions. In addition, the group is interested in the developing functionalization of nucleoside bases employing C-H direct bond activation.
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