Oxidation nucleic bases

The kinetics and mechanisms of the oxidation of DNA, nucleic acid sugars, and nucleotides by [Ru(0)(tpy)(bpy)] and its derivatives have been reported. " The Ru =0 species is an efficient DNA cleavage agent it cleaves DNA by sugar oxidation at the 1 position, which is indicated by the termini formed with and without piperidine treatment and by the production of free bases and 5-methylene-2(5//)-furanone. Kinetic studies show that the I -C— activation is rate determining and a hydride transfer mechanism is proposed. The Ru =0 species also oxidizes guanine bases via an 0x0 transfer mechanism to produce piperidine-labile cleavages. 

The interaction of the anti-tumour antibiotic bleomycin with DNA under conditions of limiting oxygen results in the production of a free nucleic base and an oxidatively damaged sugar-lesion. Studies on d(CGCTGCGT) demonstrate... 

Radical attack of nucleic bases in DNA and RNA results in their hydroxylation, disorders their regular package and decreases stability of the macromolecules with subsequent fragmentation. Actually, in cells with marked oxygen metabolism oxidative modification of nucleic acids takes place in amount exceeding ten thousand hits a day [5]. However, most of them have no after-effects for cell viability demonstrating the presence of specific cellular antioxidant defense repare system. 

Hydroxyadenosine is a naturally occurring oxidized nucleic acid adduct. N NMR chemical shifts and coupling constants indicate that the modified base exists in the 8-keto forrn. The pH dependence of the " N NMR spectra showed the presence of two pK values, 2.9 and 8.7, corresponding to protonation at N-1 and ionization at N-7, respectively. The N-7 ionization results in the formation of an 8-enolate structure. Unusual values of the H and " .N resonances of the NH2 group indicate an unfavorable steric or electronic interaction between the NH2 group and the adjacent N -H proton. 

The synthesis of a nucleotide-like phosphoramidite building block in which the nucleic base has been replaced by a tert-butyldimethylsilyl-protected styrene glycol (47) has been described. After its incorporation in an oligonucleotide by automated synthesis, the terminal alcohol has been oxidized with NaI04 after fluoride deprotection. A similar phosphoramidate in which the nucleic base has been replaced by an alkyl diol (48) has been incorporated in an oligonucleotide and further conjugated with biotin after oxidation to the aldehydic functional-ity. ... 

Cao, H. and Wang, Y. (2007) Quantification of oxidative single-base and intrastrand cross-link lesions in unmethylated and CpG-methylated DNA induced by Fenton-type reagents. Nucleic Acids Res., 35, 4833-4844. 

Strong bases hydrolyze nucleic bases slowly and ammonia is released. Acids, however, often stabilize the urea-type heterocycles. The basic lactam oxygen is protonated and converts the bases to aromatic systems (compare with Scheme 8.5.4). The C=C double bonds can usually be removed by catalytic hydrogenation or Michael addition of hydride or other nucleophiles (Scheme 8.5.1). Oxidation with peracids, on the other hand, usually gives N-oxides rather than epoxides (Suhadolnik, 1979 Shabarova and Bogdanov, 1994). 

Jaruga P, Dizdaroglu M (1996). Repair of products of oxidative DNA base damage in human cells. Nucleic Acids Res. 24 1389-1394. 

Human tissues can synthesize purines and pyrimidines from amphibolic intermediates. Ingested nucleic acids and nucleotides, which therefore are dietarily nonessential, are degraded in the intestinal tract to mononucleotides, which may be absorbed or converted to purine and pyrimidine bases. The purine bases are then oxidized to uric acid, which may be absorbed and excreted in the urine. While little or no dietary purine or pyrimidine is incorporated into tissue nucleic acids, injected compounds are incorporated. The incorporation of injected [ H] thymidine into newly synthesized DNA thus is used to measure the rate of DNA synthesis. 

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],... 

Digital storage and retrieval of chemical information is found in the nucleic adds where the basic digital operation is a two state 2/3 process (2 versus 3 hydrogen bonds in A T and G C base pairs respectively) corresponding to the usual 0/1 commutation of electronic computers. It may also be envisaged for multisite receptors or multiredox systems possessing distinct states of site occupation or of oxidation. 

The unique practical properties of adsorption have promoted its extensive use in genetic analysis. The disadvantages of adsorption with respect to covalent immobihzation are mainly that (1) nucleic acids may be readily desorbed from the substrate, and (2) base moieties may be unavailable for hybridization if they are bonded to the substrate in multiple sites [34]. However, the electrochemical detection strategy based on the intrinsic oxidation of DNA requires the DNA to be adsorbed in close contact with the electrochemical substrate by multi-point attachment. This multi-site attachment of DNA can be thus detrimental for its hybridization but is crucial for the detection based on its oxidation signals. 

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