NMR conformational analysis of DNA duplexes containing diol epoxide adducts of polycyclic aromatic hydrocarbons

The principal adducts formed between DNA and polycyclic aromatic hydrocarbon diol epoxides result from N-alkylation of the exocyclic amino groups of the purine bases by the benzylic carbon atom of the epoxide. To date, the solution conformations of mon than a dozen alkylated DNA duplexes have been examined by 2D NMR spectroscopy. For trans opened diol epoxides, oligomer duplexes containing N-2-adducts at deoxyguanosine have the hydrocarbon residue lying in the minor groove whereas those containing N-6-adducts at deoxyadenosine have the hydrocarbon intercalated within the DNA helix. Absolute configuration at the site of attachment appears to be a major determinant in establishing whether the hydrocarbon lies to the 3'- or the 5'-side of the adducted base. For trans opened deoxyadenosine adducts with R-absolute configuration, the hydrocarbon residue is positioned toward the 5'-end of the adducted strand whereas trans opened deoxyguanosine adducts with R-absolute configuration have the hydrocarbon located toward the 3'-end of the adducted strand.