Mispairing of A Site Specific Major Groove (2S,3s)-N-6(2,3,4-trihydroxybutyl)-2 '-Deoxyadenosyl Dna Adduct of Butadiene Diol Epoxide with Deoxyguanosine: Formation of A Da(Anti)Center Dot Dg(Anti) Pairing Interaction

The (2S,3S)-N-6-(2,3,4-trihydroxybutyl)-2'-deoxyadenosyl (BDT) adduct arising from alkylation of adenine N-6 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 X(6.)G(17) was oriented in a "face-to-face" orientation, in which both the modified nucleotide X-6 and its complement G(17) were intrahelical and in the anti conformation about the glycosyl bond. Hydrogen bonding was suggested between X-6 N1 and G(17) N1H and between X-6 (NH)-H-6 and G(17) O-6. 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].