Application of NMR Spectroscopy In Chemical And Biochemi

Diabetes, Digestive, Kidney Diseases

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Abstract

A major mission of this group involves the basic research and service functions of NMR instrumentation provided to NIDDK scientists of the Laboratory of Bioorganic Chemistry, Laboratory of Medicinal Chemistry, other NIH laboratories and, to a limited extent, to scientists of other institutes. In the past year, we made a major upgrade of a 15 years old console with a new state-of-the-art console and a cryo-probe for our 500 MHz NMR spectrometer. We also purchased a new 600 MHz spectrometer. Collaborative projects that use these two high field instruments include 1)structural elucidation of biologically active substances isolated from natural sources (in collaboration with Dr. John Daly's group), 2) conformational studies of structurally altered DNAs resulting from chemical modification by diolepoxides metabolically formed from known chemical carcinogens, such as benzo[a]pyrene (BaP) (in collaboration with Dr. Donald Jerina's group) and 3) conformational studies of a r(AUUCU)9 repeat responsible for spinocerebellar ataxia type 10 (in collaboration with Dr. Karen Usdin's group). The NMR results suggest that the r(AUUCU)9 repeat forms an unusual hair-pin structure with equal numbers of A-U and U-U base pairs. It is hoped that the information obtained in the benzo[a]pyrene diolepoxide DNA adducts study shall shed some light on the structural role of these carcinogens may play in the cell transformation.