A conformational analysis of the (+) anti BPDE adduct to the guanine amino group of dCpdG.
The (+) anti isomer of benz[a]pyrene diol epoxide (BPDE), 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenz [a] pyrene has been identified as the probable tumorigenic lesion in mammalian systems. It forms a predominant adduct with DNA at N2 of guanine. In order to elucidate its conformation in atomic resolution detail, minimized conformational potential energy calculations were performed for the adduct with dCpdG. A global conformation search involving about 1000 trials was made. The lowest energy conformation had stacking between the hydrocarbon and the adjacent cytidine, in agreement with CD studies on modified GpU and UpG. This conformer differed from the B form most notably in the guanine glycosidic torsion, which is high anti. The next lowest energy form had torsion angles like the B form, with guanine-cytidine stacking. These two conformers differ in energy by only 2.1 kcal./mole, suggesting that their relative stability could easily be reversed in larger polymers, or under specific environmental conditions. Other conformations, with base-hydrocarbon or base-base stacking are also found, at somewhat higher energies. The Z form is at 7.8 kcal./mole. Thus, this adduct stabilizes the B form, in contrast with the N2 linked AAF adduct, which stabilizes the Z conformation.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D001665:Binding Sites; D003845:Deoxycytosine Nucleotides; D003849:Deoxyguanosine / Q000031:analogs & derivatives*; D004101:Dihydroxydihydrobenzopyrenes; D004563:Electrochemistry; D008968:Molecular Conformation; D013237:Stereoisomerism; D013816:Thermodynamics
D003845:Deoxycytosine Nucleotides; D004101:Dihydroxydihydrobenzopyrenes; C037781:deoxycytidylyl-(3'-5')-deoxyguanosine; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003849:Deoxyguanosine