Mispairing of a site specific major groove (2S,3S)-N⁶-(2,3,4- trihydroxybutyl)-2′-deoxyadenosyl DNA adduct of butadiene diol epoxide with deoxyguanosine: Formation of a dA(anti)·dG(anti) pairing interaction

The (2S,3S)-N⁶-(2,3,4-trihydroxybutyl)-2′-deoxyadenosyl (BDT) adduct arising from alkylation of adenine N⁶ by butadiene diol epoxide (BDE) was placed opposite a mismatched deoxyguanosine nucleotide in the complementary strand of the oligodeoxynucleotide 5′-d(CGGACXAGAAG)- 3′-5′-d(CTTCTGGTCCG)-3′. This oligodeoxynucleotide contains codon 61 (underlined) of the human N-ras protooncogene. The BDT adduct was at the second position of codon 61, and this was named the ras61 S,S-BDT-(61,2) A·G adduct. NMR spectroscopy revealed the presence of two conformations of the adducted mismatched duplex. In the major conformation, the mismatched base pair X⁶·G¹⁷ was oriented in a "face-to-face" orientation, in which both the modified nucleotide X⁶ and its complement G¹⁷ were intrahelical and in the anti conformation about the glycosyl bond. Hydrogen bonding was suggested between X⁶ N1 and G¹⁷ N1H and between X⁶ N ⁶H and G¹⁷ O⁶. The presence of the BDT moiety allowed formation of a stable A·G mismatch pair. The identity of the minor conformation could not be determined. If not repaired, the resulting mismatch pair would generate A→C mutations, which have been associated with this adenine N⁶ BDT adduct [Carmical, J. R., Nechev, L. N., Harris, C. M., Harris, T. M., and Lloyd, R. S. (2000) Env. Mol. Mutagen. 35, 48-56].