Solution conformation of the N-(deoxyguanosin-8-yl)-1-aminopyrene ([AP]dG) adduct opposite dC in a DNA duplex
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
- Univ. of Connecticut, Storrs, CT (United States); and others
Combined NMR-molecular mechanics computational studies were undertaken on the C{sup 8}-deoxyguanosine adduct formed by the carcinogen 1-nitropyrene embedded in the d(C5-[AP]G6-C7){center_dot}d(G16-C17-G18) sequence context in a 11-mer duplex, with dC opposite the modified deoxyguanosine. The exchangeable and nonexchangeable protons of the aminopyrene moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H{sub 2}O and D{sub 2}O solution. There was a general broadening of several proton resonances for the three nucleotide d(G15-C17-G18) segment positioned opposite the [AP]dG6 lesion site resulting in weaker NOEs involving these protons in the adduct duplex. The solution conformation of the [AP]dG{center_dot}dC 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by upper and lower bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space. 73 refs., 8 figs., 2 tabs.
- DOE Contract Number:
- AC05-96OR22464
- OSTI ID:
- 508206
- Journal Information:
- Biochemistry (Eaton), Journal Name: Biochemistry (Eaton) Journal Issue: 39 Vol. 35; ISSN 0006-2960; ISSN BICHAW
- Country of Publication:
- United States
- Language:
- English
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