TY - JOUR
T1 - An internal fluorene model for iodo-N-2-acetylaminofluorene modified DNA
AU - Broyde, S.
AU - Hingerty, B.
N1 - Funding Information:
This work was supported jointly by American Cancer Society Institutional Grant to New York University, IN.14V (SB), NIH Grant 1RO1 CA28038°02 (SB), DOE Contract #DE-ACO2-81 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 (BID. We thank Professor Robert Shapiro and Professor D. Grunberger for helpful and interesting discussions.
PY - 1983/10/15
Y1 - 1983/10/15
N2 - Minimized conformational potential energy calculations have been performed for the 7-iodo (AAIF) and 7-fluoro (AAFF) derivatives of N-2-acetylaminofluorene (AAF), linked covalently to guanine C-8 in dCpdG. Both the iodo and the fluoro derivatives are carcinogenic and mutagenic. The lowest energy forms on the dinucleoside monophosphate level have syn guanine and fluorene-cytidine stacking. However, the iodo adduct cannot adopt this conformation in larger polymers, according to earlier experimental studies (Fuchs et al., Biochemistry, 15 (1976) 3347) and model building, because of iodine's large Van der Waal's radius. Therefore, a model consistent with all the experimental evidence, incorporating the second lowest energy conformation in B form duplex (dCdG)3 was constructed. In this model the modified guanine is syn, yet still stacked with the adjacent cytidine in one direction, the fluorene is located primarily at the helix interior between the base pairing sites, rupturing two base pairs, and the iodine atom and its adjoining ring protrude to the helix exterior.
AB - Minimized conformational potential energy calculations have been performed for the 7-iodo (AAIF) and 7-fluoro (AAFF) derivatives of N-2-acetylaminofluorene (AAF), linked covalently to guanine C-8 in dCpdG. Both the iodo and the fluoro derivatives are carcinogenic and mutagenic. The lowest energy forms on the dinucleoside monophosphate level have syn guanine and fluorene-cytidine stacking. However, the iodo adduct cannot adopt this conformation in larger polymers, according to earlier experimental studies (Fuchs et al., Biochemistry, 15 (1976) 3347) and model building, because of iodine's large Van der Waal's radius. Therefore, a model consistent with all the experimental evidence, incorporating the second lowest energy conformation in B form duplex (dCdG)3 was constructed. In this model the modified guanine is syn, yet still stacked with the adjacent cytidine in one direction, the fluorene is located primarily at the helix interior between the base pairing sites, rupturing two base pairs, and the iodine atom and its adjoining ring protrude to the helix exterior.
KW - Conformation
KW - Iodo-N-2-acetylaminofluorene
KW - Modified DNA
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U2 - 10.1016/0009-2797(83)90148-5
DO - 10.1016/0009-2797(83)90148-5
M3 - Article
C2 - 6640786
AN - SCOPUS:0021015521
SN - 0009-2797
VL - 47
SP - 69
EP - 78
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 1
ER -