The nonmutagenic (R)- and (S)-beta-(N-6-adenyl)styrene oxide adducts are oriented in the major groove and show little perturbation to DNA structure

Conformations of (R)-beta-(N-6-adenyl)styrene oxide and (S)-beta-(N-6-adeny l)styrene oxide adducts at position X-6 in d(CGGACXAGAAG)(.)d(CTTCTTGTCCG), incorporating codons 60, 61 (underlined), and 62 of the human N-ras protoo ncogene, were refined from H-1 NMR data. These were designated as the beta -R(61,2) and beta -S(61,2) adducts. A total of 533 distance restraints and 162 dihedral restraints were used for the molecular dynamics calculations o f the beta -S(61,2) adduct, while 518 distances and 163 dihedrals were used for the beta -R(61,2) adduct. The increased tether length of the beta -add ucts results in two significant changes in adduct structure as compared to the corresponding alpha -styrenyl adducts [Stone, M. P., and Feng, B. (1996 ) Magn. Reson. Chem. 34, S105-S114]. First, it reduces the distortion intro duced into the DNA duplex. For both the beta -R(61,2) and beta -S(61,2) add ucts, the styrenyl moiety was positioned in the major groove of the duplex with little steric hindrance. Second, it mutes the influence of stereochemi stry at the alpha -carbon such that both the beta -R(61,2) and beta -S(61,2 ) adducts exhibit similar conformations. The results were correlated with s ite-specific mutagenesis experiments that revealed the beta -R(61,2) and be ta -S(61,2) adducts were not mutagenic and did not block polymerase bypass.