Solution conformation of the (-)-trans-anti-benzo[c]phenanthrene-dA ([BPh]dA) adduct opposite dT in a DNA duplex: Intercalation of the covalently attached benzo[c]phenanthrenyl ring to the 3{prime}-side of the adduct site and comparison with the (+)-trans-anti-[BPh]dA opposite dT stereoisomer
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States); and others
This paper reports on NMR-molecular mechanics structural studies of the (-)-trans-anti-benzo[c]phenanthrene-dA adduct positioned opposite dT in the sequence context of the d(C1-T2-C3-T4-C5-[BPh]A6-C7-T8-T9-C10-C11){center_dot}d(G12-G13-A14-A15-G16-T17-G18-A19-G20-A21-G22) duplex (designated as the (-)-trans-anti-[BPh]dA6{center_dot}dT 11-mer duplex). This adduct is derived from the covalent binding of (-)-1,2-dihydroxy-3,4-epoxy- 1,2,3,4-tetrahydro-benzo[c]phenanthrene[(-)-anti-BPhDE] to N{sup 6} of dA6 in this duplex sequence. The benzo[c]phenanthrenyl and nucleic acid exchangeable and nonexchangeable protons were assigned in the predominant conformation following analysis of two-dimensional NMR data sets in H{sub 2}O and D{sub 2}O buffer solution. The solution structure of the (-)-trans-anti-[BPh]dA{center_dot}dT 11-mer duplex has been determined by incorporating intramolecular and carcinogen-DNA proton-proton distances defined by lower an upper bounds deduced from NOESY data sets as restraints in molecular mechanics computations in torsion angle space. 52 refs., 9 figs., 2 tabs.
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- FG02-90ER60931; AC05-84OR21400
- OSTI ID:
- 469831
- Journal Information:
- Biochemistry (Eaton), Journal Name: Biochemistry (Eaton) Journal Issue: 4 Vol. 34; ISSN 0006-2960; ISSN BICHAW
- Country of Publication:
- United States
- Language:
- English
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