TY - JOUR
T1 - A conformational analysis of the (+) anti bpde adduct to the guanine amino group of dcpdg
AU - Hingerty, B.
AU - Broyde, S.
N1 - Funding Information:
This work was supported jointly by PHS Grant #1 R01 CA28038-03, awarded by the National Cancer Institute, DHHS (SB), DOE Contract #DE-AC01-81 ER60015 (SB), and by the Office of Health and Environmental Research; U.S. Department of Energy, under contract W-7405-eng-26 with the Union Carbide Corporation (BH). We thank Profs. Robert Shapiro, D. Grunberger and K. Frenkel for many interesting discussions.
PY - 1983/12
Y1 - 1983/12
N2 - The (+) anti isomer of benz[a]pyrene diol epoxide (BPDE), 7β,8α-dihydroxy-9α,10α-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.
AB - The (+) anti isomer of benz[a]pyrene diol epoxide (BPDE), 7β,8α-dihydroxy-9α,10α-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.
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U2 - 10.1080/07391102.1983.10507492
DO - 10.1080/07391102.1983.10507492
M3 - Article
C2 - 6443880
AN - SCOPUS:0020958663
SN - 0739-1102
VL - 1
SP - 905
EP - 912
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
IS - 4
ER -