PURCHASE OF A 600 MHZ NMR SPECTROMETER

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The goal of this proposal is to purchase a 600 MHz NMR spectrometer to enhance ongoing research at Wayne State University in the areas of A) ribosomal RNA structure and function, B) RNA-protein and RNA-antibiotic complex structure, C) DNA-carcinogen adduct structure, D) protein structure determination of alpha-1,3- galactosyltransferase and proteins involved in metal transport and resistance, and E) assay of metabolite concentrations in neuronal cell lysates. These topics represent the research of six well-established NIH-funded laboratories. At least 85% of the time on the new 600 MHz NMR will be devoted to these research projects. The remaining instrument time will be devoted to other active areas of research at Wayne State University including: the structure of proteins with bound peptide mimics, polymer chemistry, natural products chemistry, mechanistic organic chemistry, and RNase III-RNA interactions. The only instrument at Wayne State University that is suitable for studying biomolecules is a Varian UNITY 500 MHz NMR. The console on this instrument is obsolete and it cannot run several modern pulse sequences. In addition, only half of the time on this instrument is available for studies of biomolecules. The addition of a 600 MHz NMR will significantly extend our NMR capabilities and will meet the growing demand at Wayne State University for time on a high-field NMR instrument. The increased field strength and improved console and probe design will result in a approximate 30-40% improvement in signal-to-noise ratio, will reduce spectral artifacts, and will improve spectral resolution by 20% in each dimension (44% improvement in 2D-NMR and 73% improvement in 3D-NMR). The improve performance of a 600 MHz NMR spectrometer and availability of more instrument time will increase both the quality and quantity of NMR data. This in turn will extend our ability to study the structures of larger biomolecules. Due to the large increase in the number of groups at Wayne State University performing biomolecular NMR, a rigorous training program has been initiated. New users are trained by Dr. Ksebati on the proper use of NMR instrumentation. Dr. SantaLucia holds weekly meetings on the theory and practice of NMR, which are consistently attended by more than 20 students and postdoctoral fellows. Students are trained from elementary NMR through advanced theory, including density matrix and product operator descriptions of NMR and pulse sequence programming.