Release of Superoxide from Nucleoside Peroxyl Radicals, a Double-Edged Sword?

Tallman, Keri A.; Tronche, Christopher; Yoo, Dong Jin; Greenberg, Marc M.

doi:10.1021/ja973200s

Cited by 56 publications

(70 citation statements)

References 31 publications

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“…This is surprising since the formation of dL, a tentative precursor to 5-MF, requires one-electron oxidation of the intermediate C1′ radical. As has been demonstrated previously (35)(36)(37), in the presence of oxygen this step proceeds through the formation and decomposition of an intermediate peroxyl radical through elimination of superoxide O 2 •-. In our experiments, the absence of oxygen only partially suppressed formation of 5-MF; therefore, another oxidant must play the role of oxygen in this anoxic system.…”

Section: Catalytic Effects Of 5-mf Releasementioning

confidence: 54%

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

et al. 2005

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Release of 5-methylene-2-furanone (5-MF), a characteristic marker of DNA deoxyribose oxidative damage at the C1′ position, was observed in significant quantities from X-irradiated DNA. This observation, which held for DNA irradiated either in aqueous solution or as a film, requires postirradiation treatment at 90° C in the presence of polyamines and divalent metal cations at biological pH. The 5-MF product was quantified by using reverse-phase HPLC. The radiation chemical yield of 5-MF comprised more than 30% of the yield of total unaltered base release. Polylysine, spermine and Be(II) showed the strongest catalytic effect on 5-MF release, while Zn(II), Cu(II), Ni(II), putrescine and Mg(II) were substantially less efficient. We have hypothesized that the 5-MF release from irradiated DNA occurs through catalytic decomposition of the 2′ -deoxyribonolactone (dL) precursor through two consecutive β -and δ -phosphate elimination reactions. A stepwise character of the process was indicated by the S-shaped time course of 5-MF accumulation. If dL proves to be the precursor to 5-MF formation, it would then follow that dL is a very important lesion generated in DNA by ionizing radiation.

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Section: Catalytic Effects Of 5-mf Releasementioning

confidence: 54%

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

et al. 2005

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“…Cleavage data were fit to an exponential decay model, which was used to calculate the half-life for DNA strand scission at the damage site. Figure 6A shows the data obtained for analysis of single-stranded 2 DNA cleavage as compared with 2 hybridized with a complementary strand (15)(16)(17)(18) Although the data in Figure 6A gave preliminary insight into the rates of cleavage at deoxyribonolactone lesions, the results were complicated by the fact that two DNA products were observed ( Figure 2) and used to calculate the decay rates. Thus, it was critical to determine the rate of the first R, -elimination step as compared with the second step.…”

Section: Isolation and Maldi-tof Ms Characterization Of The Products mentioning

confidence: 99%

Half-Life and DNA Strand Scission Products of 2-Deoxyribonolactone Oxidative DNA Damage Lesions

Zheng

Sheppard

2004

Chem. Res. Toxicol.

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Reactive oxygen species lead to oxidative damage of the nucleobase and sugar components of nucleotides in double-stranded DNA. The 2-deoxyribonolactone (or oxidized abasic site) lesion results from oxidation of the C-1' position of DNA nucleotides and has been implicated in DNA strand scission, mutagenesis, and covalent cross-linking to DNA binding proteins. We previously described a strategy for the synthesis of DNA-containing deoxyribonolactone lesions. We now report an improved method for the site specific photochemical generation of deoxyribonolactone sites within DNA oligonucleotides and utilize these synthetic oligonucleotides to characterize the products and rates of DNA strand scission at the lactone lesion under simulated physiological conditions. A C-1' nitroveratryl cyanohydrin phosphoramidite analogue was synthesized and used for the preparation of DNA containing a photochemically "caged" lactone precursor. Irradiation at 350 nm quantitatively converted the caged analogue into the deoxyribonolactone lesion. The methodology was validated by RP-HPLC and MALDI-TOF mass spectrometry. Incubation of deoxyribonolactone-containing DNA under simulated physiological conditions gave rise to DNA fragmentation by two consecutive elimination reactions. The DNA-containing products resulting from DNA cleavage at the deoxyribonolactone site were isolated by PAGE and unambiguously characterized by MALDI-TOF MS and chemical fingerprinting assays. The rate of DNA strand scission at the deoxyribonolactone site was measured in single- and double-stranded DNA under simulated physiological conditions: DNA cleavage occurred with a half-life of approximately 20 h in single-stranded DNA and 32-54 h in duplex DNA, dependent on the identity of the deoxynucleotide paired opposite the lesion site. The initial alpha,beta-elimination reaction was shown to be the rate-determining step for the formation of methylene furanone and phosphorylated DNA products. These investigations demonstrated that the deoxyribonolactone site represents a labile lesion under simulated physiological conditions and forms the basis for further studies of the biological effects of this oxidative DNA damage lesion.

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“…Spectral characteristics were identical to those previously reported. [5,6] Spironucleoside 7b. Following the above reported procedure for the addition of MeLi to the cyano uridine 5 (150 mg, 0.31 mmol) and after acidic work-up, a mixture of ketone 6b and spironucleoside 7b was obtained (132 mg, 0.26 mmol, 84% yield), which were deprotected and characterized as already reported.…”

Section: '-Branched and Spironucleoside Analogues 1573mentioning

confidence: 99%

“…[5,6] Numerous cyano nucleosides have been synthesized and their pharmacological properties have been elucidated. 3'-C-cyano nucleosides are the most studied mainly due to their structural similarity to AZT and related drugs.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel 1′‐Branched and Spironucleoside Analogues

Chatgilialoglu

Ferreri

Gimisis

et al. 2004

Nucleosides, Nucleotides & Nucleic Acids

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Novel anomeric spironucleosides and 1'-cyano-2',3'-didehydro-2',3'-dideoxyuridine, a structural analogue of known anti-HIV agents, were prepared by nucleophilic addition of organolithium reagents to 1'-cyano-2'-deoxy- and 1'-cyano-2'-deoxy-2'beta-bromo-uridine derivatives, respectively. The yield and distribution of products depended on the reaction conditions, which were studied in detail. Although none of the compounds exhibited antiviral activity, two compounds displayed cytostatic activity against both murine leukemia and human T-lymphocyte cells.

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Release of Superoxide from Nucleoside Peroxyl Radicals, a Double-Edged Sword?

Cited by 56 publications

References 31 publications

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

Half-Life and DNA Strand Scission Products of 2-Deoxyribonolactone Oxidative DNA Damage Lesions

Synthesis and Biological Evaluation of Novel 1′‐Branched and Spironucleoside Analogues

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