INTEGRATED SOLID-STATE/SOLUTION NMR STUDY OF DNA

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It is proposed to use a combination of solid-state and solution NMR spectroscopy to investigate the structure and dynamics of DNA and of drugs and other agents bound to DNA. It has recently been shown that the methods for determining the conformation of the deoxyribose ring in DNA oligomers may be susceptible to errors arising from quantum-mechanical interference between dipolar cross-relaxation and the J coupling. This J coupling is used, via the Karplus equation, to determine the conformation. A new mathematical formalism is proposed to allow calculation of these interference effects. A series of experiments is proposed to evaluate the seriousness of the errors resulting from a neglect of this term; methods for correct extraction of J couplings and cross-relaxation rate constants will be developed. Solid-state NMR experiments on DNA fibers and model compounds, which originally gave the discrepant results which pointed out the existence of this interference term, will be continued, with an emphasis on observing drug binding to synthetic DNA high polymers of high molecular weight.