Hydroxyl 2-deoxyribose oxidation

Hydroxyl Radical-Mediated 2-Deoxyribose Oxidation Reactions 67... 

The product of deoxyribose oxidation at Cl, 5, could be observed by HPLC. However, it was noted that a minor amount of C4 hydroxylation may be observed as well at some residues in the loops. The oxidation of the C4 -H bond of some deoxyribose units in the single-stranded loops was due to an hydroxylation (formation of 4 -hydroxylated abasic site, 23), no 3 -phosphogly-colate were detected. The C4 oxidation mechanism was evidenced, on polyacrylamide gels, by the protection of NaBH4 toward piperidine sensitive cleavage at some T residues. 

In 1977, Kellogg and Fridovich [28] showed that superoxide produced by the XO-acetaldehyde system initiated the oxidation of liposomes and hemolysis of erythrocytes. Lipid peroxidation was inhibited by SOD and catalase but not the hydroxyl radical scavenger mannitol. Gutteridge et al. [29] showed that the superoxide-generating system (aldehyde-XO) oxidized lipid micelles and decomposed deoxyribose. Superoxide and iron ions are apparently involved in the NADPH-dependent lipid peroxidation in human placental mitochondria [30], Ohyashiki and Nunomura [31] have found that the ferric ion-dependent lipid peroxidation of phospholipid liposomes was enhanced under acidic conditions (from pH 7.4 to 5.5). This reaction was inhibited by SOD, catalase, and hydroxyl radical scavengers. Ohyashiki and Nunomura suggested that superoxide, hydrogen peroxide, and hydroxyl radicals participate in the initiation of liposome oxidation. It has also been shown [32] that SOD inhibited the chain oxidation of methyl linoleate (but not methyl oleate) in phosphate buffer. 

Pitie M, Bernadou J, Meunier B (1995) Oxidation at carbon-1 of DNA deoxyriboses by the Mn-TM-PyP/KEIS05 system results from a cytochrome P-450-type hydroxylation reaction. J Am Chem Soc 117 2935-2936... 

The degradation of 2-deoxyribose by Fenton s reagent has been conducted in acidic, neutral, and alkaline media, and in the presence and absence of hydroxyl-radical scavengers. It seems that both the substrate and the scavengers interact with the metal ions.110 Traces of Fe(II) accelerate the oxidation of carbohydrates by H202, but larger quantities of such a cation has a retarding elfect.111... 

Bernhard and co-workers have performed a series of experiments to determine the mechanisms of DNA strand breakage by direct ionization of plasmid DNA. A big surprise in this work was the discovery that the total yield of single strand breaks exceeds the yield of trapped sugar radicals. Even at very low hydration levels (2.5 waters per nucleotide residue) nearly 2/3 of the strand breaks are derived from precursors other than deoxyribose radicals [74], The authors conclude that a majority of the strand breaks observed do not result from dissociative electron capture, homolytic bond cleavage from excited states, or from hydroxyl radical attack. Rather, the authors conclude that doubly oxidized deoxyribose is responsible for the high yield of strand breaks. 

The kinetic studies also argue strongly for 1 oxidation. First, all of the nucleotides are more reactive than deoxyribose and ribose. This result can be ascribed to more effective activation of the 1 position by the nucleic acid base compared to hydroxyl, which is likely to be less electron-donating. This trend is evident even after correction of rate constants for the electrostatic binding preequilibrium. In fact, this same trend is evident in the Pt2(pop)4 rate constants. Since Pt2(pop)4 is a tetraanion, the reactions of nucleotides are actually discouraged electrostatically relative to those of the neutral sugars—yet nucleotides are more reactive by about an order of magnitude in rate constant. 

Oxidants such as hydroxyl radical or peroxynitrite also react with the 2 -deoxyribose scaffold of DNA. Each hydrogen on the 2 -deoxyribose ring is subject to free radical-mediated abstraction and subsequent diffusion-limited reaction with molecular oxygen. Each site of peroxidation leads to a separate and overlapping array of products. Following hydrogen abstraction on 2 -deoxyribose by reactive oxygen... 

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