Fate of the C-1′ peroxyl radical in the 2′-deoxyuridine system

Chatgilialoglu, Chryssostomos; Gimisis, Thanasis

doi:10.1039/a802375a

Cited by 47 publications

(29 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 97%

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

Zheng

Sheppard

2004

Chem. Res. Toxicol.

View full text Add to dashboard Cite

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.

show abstract

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

confidence: 97%

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

Zheng

Sheppard

2004

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…It corresponds to a damage in DNA that has been reported to occur under the action of different drugs, notably the enediyne antibiotics 136 -139 and by ␥-radiolysis. 140 The mode of generation, although the subject of current debate, [141][142][143] is generally considered to involve radical H-1Ј abstraction and oxydation ( Figure 16). Different generation modes and properties of this precursor radical have been recently discussed.…”

Section: Oxidized Abasic Sites: the 2-deoxyribonolactone Lesionmentioning

confidence: 99%

Abasic DNA structure, reactivity, and recognition

1999

View full text Add to dashboard Cite

“…[ [10][11][12][13] For the removal of the hydroxy group, the strategy starts from a thiocarbonyl derivative (e.g., O-arylthiocarbonate, O-thioxocarbamate, thiocarbonyl imidazole or xanthate) or a selenocarbonate. An example is provided using the Ophenylthiocarbonate 4 (Scheme 1).…”

mentioning

confidence: 99%

(Me₃Si)₃SiH: Twenty Years After Its Discovery as a Radical‐Based Reducing Agent

Chatgilialoglu

2008

Chemistry A European J

Self Cite

153

View full text Add to dashboard Cite

This Concept shows the flexibility and applicability of (Me3Si)3SiH in several synthetic transformations, such as radical reductions, consecutive radical reactions and hydrosilylation. The reactivity of (Me3Si)3SiH combines the multidisciplinary aspects of physical organic chemistry and organic synthesis, extending to polymers and materials science, as in the functionalization of flat silicon surfaces.

show abstract

Fate of the C-1′ peroxyl radical in the 2′-deoxyuridine system

Cited by 47 publications

References 25 publications

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

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

Abasic DNA structure, reactivity, and recognition

(Me₃Si)₃SiH: Twenty Years After Its Discovery as a Radical‐Based Reducing Agent

Contact Info

Product

Resources

About

Fate of the C-1′ peroxyl radical in the 2′-deoxyuridine system

Cited by 47 publications

References 25 publications

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

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

Abasic DNA structure, reactivity, and recognition

(Me3Si)3SiH: Twenty Years After Its Discovery as a Radical‐Based Reducing Agent

Contact Info

Product

Resources

About

(Me₃Si)₃SiH: Twenty Years After Its Discovery as a Radical‐Based Reducing Agent