Applications of NMR spectroscopy to studies of reactive intermediates and their interactions with nucleic acids

Harris, Thomas M.; Stone, Michael P.; Harris, Constance M.

doi:10.1021/tx00002a001

Cited by 14 publications

(8 citation statements)

References 77 publications

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“…For example, sufficient amounts of defined DNA sequence molecules can be prepared by automated synthesis methods and then characterized by X-ray crystallography and high-field NMR. The application of high-field NMR to elucidation of the three-dimensional structure of carcinogen-DNA adducts has been recently reviewed by Harris et al (119). Recombinant DNA technology provides both the methods and materials to test both old and new concepts on how DNA-reactive ligands may exert their potent biological effects.…”

Section: Experimental Measurements Of Sequence Selectivitymentioning

confidence: 99%

Sequence selectivity of DNA covalent modification

Warpehoski¹,

Hurley

1988

Chem. Res. Toxicol.

205

150

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Section: Experimental Measurements Of Sequence Selectivitymentioning

confidence: 99%

Sequence selectivity of DNA covalent modification

Warpehoski¹,

Hurley

1988

Chem. Res. Toxicol.

205

150

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“…Moreover, DNA adduct analysis by using the 32 Ppostlabeling assay could not provide structural information for the molecule of interest. High-field NMR was previously shown to be one of the valuable tools for DNA adduct analysis [26,27]. However, micro-to milligram samples of pure adduct are needed for structural elucidation, which is often impossible for in vivo studies.…”

mentioning

confidence: 99%

Liquid chromatography—tandem mass spectrometry analysis of the DNA adducts of aristolochic acids

Chan

Zheng

Cai

2007

J. Am. Soc. Mass Spectrom.

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Electrophilic attack of aristolactam-nitrenium ion by the C7 position to the exocyclic amino group in the DNA bases led to the formation of the major adducts. In this study, liquid chromatography coupled with electrospray ionization tandem mass spectrometry was applied to the study of DNA adducts of aristolochic acid (AA). When DNA (bases and CT-DNA) was incubated with AA, dG-AAI, dG-AAII, dA-AAI, dA-AAII, dC-AAI, and dC-AAII were detected and characterized. The dC adducts of AA were identified for the first time. The soft ionization technology allowed detection of the intact DNA adducts. High-resolution MS and MS-MS capabilities of a quadrupole time-of-flight mass spectrometer were shown to be efficient for DNA adducts analysis. DNA-AA adducts showed characteristic fragmentation patterns in MS-MS analysis. The dissociative loss of 116 Da from the DNA-AA adducts, which resulted from internal hydrogen transfer and cleavage at the CON glycosidic bond, provided a characteristic fragment for the structural elucidation. (J Am Soc Mass Spectrom 2007, 18, 642-650)

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“…Although NMR methods have been used extensively for this purpose (Evans et al, 1980(Evans et al, , 1984Evans & Miller, 1982;Evans & Levine, 1987Sharma & Box, 1985;Shapiro et al, 1986), the number of reported solution NMR studies of intact arylamine-DNA adducts at the duplex level is small (Norman et al, 1989;Cho et al, 1992;O'Handley et al, 1993). This is due in part to the spectral complexities encountered in the proton NMR spectra of modified duplex oligomers (Harris et al, 1988) and to the technical difficulties in preparing carcinogen-modified oligonucleotides (Basu & Essigmann, 1988).…”

mentioning

confidence: 99%

NMR structural studies of a 15-mer DNA duplex from a ras protooncogene modified with the carcinogen 2-aminofluorene: conformational heterogeneity

Cho¹,

Beland²,

Marques³

1994

Biochemistry

120

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Proton NMR studies were conducted on the complementary 15-mer DNA duplex, d(5'-TACTCTTCTT[AF]GACCT).d (5'-AGGTCAAGAAGAGTA) (designated as the AF-modified duplex). The sequence represents a portion of the mouse c-Ha-ras protooncogene and was selectively modified to contain a single N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF) adduct at the deoxyguanosine corresponding to the first base of codon 61. The AF-modified duplex was found to exist in multiple conformations, with one being predominant (approximately 60%). The exchangeable and nonexchangeable protons belonging to the major conformer were sufficiently well-resolved to allow the assignment of the majority of the base and sugar protons. The one-dimensional proton spectra, as well as the NOE cross-peak patterns associated with this conformer of the AF-modified duplex both in H2O and D2O spectra, were strikingly similar to those observed for the major conformer of an analogous duplex containing N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) in the same position [Cho, B.P., Beland, F. A., & Marques, M. M. (1992) Biochemistry 31, 9587-9602]. The experimental results suggest that the AF- and ABP-modified duplexes adopt essentially identical major conformations, with each arylamine moiety being positioned in the major groove of a slightly disturbed B-type DNA duplex. Nonetheless, the absence of specific NOE cross peaks in the vicinity of the modification site indicates that the local structural perturbation is more severe in the AF-modified duplex. Although insufficient data precluded a detailed characterization of the minor conformers of the AF-modified duplex, the observation of significant shielding of the AF aromatic protons suggests a more dramatic structural alteration at the adduct site, possibly involving extensive stacking with the neighboring bases. The higher content (30-40%) of the minor conformers observed for the AF-modified duplex contrasted with the low contribution (5-10%) of similar structures in the ABP-modified duplex and may be attributed to a better overlapping efficiency of the planar AF ring with the nearby bases. Since the significant local perturbation observed in the minor conformers could provide a possible mechanism for mutations, our results support the view that the structural differences in the arylamine fragments of otherwise identical adducts have a direct influence on the conformational heterogeneities, which in turn may play a significant role in arylamine carcinogenesis.

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Applications of NMR spectroscopy to studies of reactive intermediates and their interactions with nucleic acids

Cited by 14 publications

References 77 publications

Sequence selectivity of DNA covalent modification

Sequence selectivity of DNA covalent modification

Liquid chromatography—tandem mass spectrometry analysis of the DNA adducts of aristolochic acids

NMR structural studies of a 15-mer DNA duplex from a ras protooncogene modified with the carcinogen 2-aminofluorene: conformational heterogeneity

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