Nucleic acid bases, oxidation

Phenylglyoxal and alkoxyphenylglyoxals react selectively with the guanine moiety of nucleosides and nucleotides in phosphate buffer (pH 7.0) at 37°C for 5-7 min to give the corresponding fluorescent derivatives [12-15], as shown in Figure 6. Other nucleic acid bases and nucleotides (e.g., adenine, cytosine, uracil, thymine, AMP, CMP) do not produce derivatives under such mild reaction conditions. The fluorescent derivative emits chemiluminescence on oxidation with di-methylformamide (DMF) and H202 at pH 8.0-12 [14, 15],... 

Oxidative DNA Damage From Hole Injection to Oxidative Modifications of Nucleic Acid Bases and Their Biological Impact... 

Guanine is the most easily oxidizable natural nucleic acid base [8] and many oxidants can selectively oxidize guanine in DNA [95]. Here, we focus on the site-selective oxidation of guanine by the carbonate radical anion, COs , one of the important emerging free radicals in biological systems [96]. The mechanism of COs generation in vivo can involve one-electron oxidation of HCOs at the active site of copper-zinc superoxide dismutase [97, 98], and homolysis of the nitrosoperoxycarbonate anion (0N00C02 ) formed by the reaction of peroxynitrite with carbon dioxide [99-102]. 

The observation of currents attributable to the faradaic electrochemistry of nucleic acids was pioneered by Palecek and coworkers who studied DNA adsorbed on mercury or carbon electrodes [13]. The signals detected by Palecek were attributable to oxidation of the purines, which produced signals indicative of irreversible processes involving adsorbed bases. These reactions were used as a basis for electrochemical analysis of DNA. Kuhr and coworkers later showed that similar strategies could be developed for analysis of nucleic acids via oxidation of sugars at copper electrodes [14-16]. 

Moschel RC, Behrman EJ (1974) Oxidation of nucleic acid bases by potassium peroxodisulfate in alkaline aqueous solution. J Org Chem 39 1983-1989... 

Barciszewski J, Barciszewska MZ, Siboska G, Rattan SIS, Clark BFC (1999) Some unusual nucleic acid bases are products of hydroxyl radical oxidation of DNA and RNA. Mol Biol Reports 26 231-238... 

Contrary to H-bonded nucleic acid base pairs discussed in the previous section, the nature of intermolecular interactions in complexes of stacked bases was analyzed more extensively. The values of minimal, maximal, and average total stabilization energies, corrected for BSSE, for a set comprising over 80 stacked bases, are plotted in Fig. 20.1. In the case of guanine-adenine and adenine-cytosine complexes, the results are presented for two sequence contexts, i.e., A/G-G/A and A/C-C/A. The symbol AA denotes the 2-oxo-adenine - complexes of oxidized bases, and this... 

Another interesting topic, yet not well understood, is how the oxidation of nucleic acid bases influences the stability of DNA, and in particular, to what extent it changes the nature of intermolecular interactions. The biological consequences of damage to nucleic acids have been the subject of numerous experimental studies [39, 40], DNA may be exposed in vivo to hydroxyl radicals produced during endogenic cellular processes [41,42], Increased concentration of modified nucleic acid base derivatives (i.e., 8-oxo-guanine, 2-oxo-adenine) in cancer cells has been observed. For this reason, the analysis of the influence of modification of nucleic acid bases by hydroxyl radical on the nature of intermolecular interactions seems to be very advisable. The results of calculations presented in Fig. 20.2 show that... 

When oxides of nitrogen come in contact with water, both nitrous and nitric acids are formed (18) (Table IV). Toxic reactions may result from pH decrease. Other toxic reactions may be a consequence of deamination reactions with amino acids and nucleic acid bases. Another consideration is the reactions of oxides of nitrogen with double bonds (Table IV). The cis-trans isomerization of oleic acid exposed to nitrous acid has been reported (19). Furthermore, the reaction of nitrogen dioxide with unsaturated compounds has resulted in the formation of both transient and stable free radical products (20, 21) (Table V). A further possibility has been raised in that nitrite can react with secondary amines to form nitrosamines which have carcinogenic properties (22). Thus, the possible modes of toxicity for oxides of nitrogen are numerous and are not exhausted by this short list. 

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. 

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