ACQUISITION OF A 400 MHZ NMR SPECTROMETER FOR RESEARCH

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This proposal is a request for the funds required to purchase a 400 MHz NMR spectrometer to expand and update current capabilities in NMR instrumentation at Cornell University. The requested spectrometer will be devoted to structural studies of small molecules in liquids and will provide modern techniques to a core group of NIH-supported users. The spectrometer will be housed in the Chemistry Department NMR Facility, which provides instrumentation and training to almost 200 students and researchers from the university community and local industry. Five NIH- funded Cornell faculty members require access to this spectrometer to carry out a variety of health-related projects. Professor B. Ganem (Principal Investigator) will study (1) potential inhibitors of chorismate mutase/prephenate dehydratase involved in the shikimic acid pathway, (2) the synthesis of glycosidase inhibitors, (3) the synthesis of purine nucleoside phosphorylase inhibitors important for the treatment of AIDS, and (4) inhibitors of glutathione and trypanothione reductases. Professor T. Begley will investigate enzyme function and mechanism by using NMR spectroscopy to elucidate the structure of products of enzyme-catalyzed reactions. These reactions include the (6) thiamin biosythetic pathway, (7) enzymatic repair of UV-irradiated DNA in bacterial spores, (8) the mechanism and inhibition of prolyl-4- hydroxylase, and (9) the biosynthesis of taxol. Professor J. Clardy will investigate natural products from novel sources including (10) anticancer compounds isolated from endophytic fungi and (11) compounds displaying antibiotic properties toward the plant pathogens responsible for fire blight. Professor D. B. Collum will investigate (5) organolithium solvation and aggregation using 6 Li-detected triple- resonance spectroscopy. Professor J. Meinwald will continue to pioneer the field of chemical ecology by exploring (12) biologically active compounds isolated from insect sources.