CHEM & BIOL OF DNA ADDUCT: ANALYSIS OF DNA ADDUCTS HAVING MULTIPLE CONFORMATIONS

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Conformational heterogeneity is emerging as a common feature of oligodeoxynucleotides adducted with chemical carcinogens. Spectroscopically, conformational heterogeneity introduces several problems. First, resonance signals arising from each conformation present in the sample must be individually resolved and identified. Second, conformational heterogeneity reduces the effective sample concentration. Third, methodology for structural refinement of these adducts is not well-developed. Ultra high field NMR provides an attractive method for examining conformationally labile samples because of its extraordinary resolving power and sensitivity, to help identify and assign resonances which arise from conformation exchange. We propose to take advantage of this to develop a better understanding of the conformational equilibria involved for styrene oxide and benzo[a]pyrene adducts of adenine, in an effort to correlate adduct structure with function.