title: Covalent binding of (+)- and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyr ene to B and Z DNAs.
abstract: Circular dichroism (CD) as well as absorption spectral measurements reveals that poly(dG-m5dC).poly(dG-m5dC) suffers more extensive covalent modification by (+)-dihydroxy-anti-epoxybenzo[a]pyrene [(+)-anti-BPDE] than its unmethylated counterpart and that the covalently attached pyrenyl moiety exhibits stronger stacking interactions with the bases in the methylated polymer as suggested by the much larger pyrenyl spectral red shifts, most likely the consequence of intercalation. Stereoselective binding properties of these polymers are evidenced by the much reduced preference for the (-) enantiomer. Modifications due to (+)-anti-BPDE on the 50 microM hexaamminecobalt induced Z DNAs are much less pronounced and much less stereoselective, with the pyrenyl spectral characteristics being distinct from those of the B form. Salt titrations on the (+)-anti-BPDE modified poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) indicate much reduced cooperativity on the B to Z transition when compared to the unmodified counterparts. Evidence also suggests that covalent modification by anti-BPDE inhibits the B to Z conversion of base pairs in its immediate vicinity, presumably through intercalative stabilization of the B conformer at high salt. In contrast to stabilizing the B conformation for the proximal base pairs, covalent lesion by (+)-anti-BPDE appears to destabilize distal base pairs with the consequence of kinetic facilitation of B to Z transformation for these regions. Interesting differential effects on the reverse Z to B transforming abilities of these two enantiomers are observed with the covalent binding of the (-) isomer showing higher potency for inducing such conversion.
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D001580:Benzopyrenes; D002273:Carcinogens; D002942:Circular Dichroism; D007700:Kinetics; D009690:Nucleic Acid Conformation; D011089:Polydeoxyribonucleotides; D013329:Structure-Activity Relationship
chemical_list: D001580:Benzopyrenes; D002273:Carcinogens; D011089:Polydeoxyribonucleotides; C016681:poly(dG).poly(dC); C029988:poly(dG-m(5)dC).poly(dG-m(5)dC); D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide