Cytosine 3-oxide

Alloxan, another minor product of cytosine oxidation found in DNA, can also undergo decarboxylation to yield 5-hydroxyhydantoin [37,40]. Similarly, thymine can be oxidised to 5-methyl-5-hydroxyhydantoin (Scheme 7). 

Table III Hyperfine Coupling Parameters for Cytosine Oxidation Products ...

Mechanism of oxidation of purine bases (adenine and guanine) and pyrimidine bases (uracil, thymine and cytosine) in presence of NaOH by bromamine-B(BAB) has been investigated. The reactions follow identical kinetics for all the bases, being first order dependence on [BAB]o and fractional order each in [substrate]o and [NaOH]. Addition of the reaction product retards the rate and the dielectric effect is positive. Variation of ionic strength and addition of halide ions had no effect on the rate. Proton inventory studies were made in H2O-D2O mixtures for adenine and cytosine. Oxidation products were identified and activation parameters were evaluated. An isokinetic relationship is observed with p = 336 K indicated that enthalpy factors control the rate. The rate of oxidation of purines is in the order guanine > adenine while in case of pyrimidines the order is thymine > uracil > cytosine. A suitable mechanism is proposed and discussed. 

The aldehyde oxidoreductase from Desulfovibrio gigas shows 52% sequence identity with xanthine oxidase (199, 212) and is, so far, the single representative of the xanthine oxidase family. The 3D structure of MOP was analyzed at 1.8 A resolution in several states oxidized, reduced, desulfo and sulfo forms, and alcohol-bound (200), which has allowed more precise definition of the metal coordination site and contributed to the understanding of its role in catalysis. The overall structure, composed of a single polypeptide of 907 amino acid residues, is organized into four domains two N-terminus smaller domains, which bind the two types of [2Fe-2S] centers and two much larger domains, which harbor the molybdopterin cofactor, deeply buried in the molecule (Fig. 10). The pterin cofactor is present as a cytosine dinucleotide (MCD) and is 15 A away from the molecular surface,... 

Because synthesis of l-(2-deoxy-2-fluoro-)S-D-arabinofuranosyl)cytosine (744, FAC), an elementary arabino type of nucleoside having a growth-inhibitory effect against L 1210 leukemia in mice, through direct introduction of a fluorine atom in the 2 - up (arabino) position was difficult, compound 744 was prepared by condensation of trimethylsilylated A -acetylcytosine with 3-0-acetyl-5-(7-benzoyl-2-deoxy-2-fluoro-D-arabin-ofuranosyl bromide (742), which had been prepared by periodate oxidation of 6-0-benzoyl-3-deoxy-3-fluoro-D-glucofuranose (741). Similar condensa-... 

Schimanski, A., Ereisinger, E., Erxleben, A. and Lippert, B. (1998) Interactions between [AuX4] (X = Cl, CN) and cytosine and guanine model nucleobases salt formation with (hemi-) protonated bases, coordination, and oxidative degradation of guanine. Inorganica Chimica Acta, 283, 223. 

One-Electron Oxidation Reactions of Cytosine and 5-methylcytosine DNA Base... 

Deoxycytidine (dCyd) (14 in Scheme 2) is also an excellent target for one-electron oxidation reactions mediated by triplet excited menadione. On the basis of extensive identification of dCyd photooxidation products, it was concluded that this nucleoside decomposes by competitive hydration and deprotonation reactions of cytosine radical cations with yields of 52% and 40%, respectively [53]. It was also found, on the basis of 180 labeling experiments, that hydration of cytosine radical cations (15) predominantly occurs... 

Other degradation products of the cytosine moiety were isolated and characterized. These include 5-hydroxy-2 -deoxycytidine (5-OHdCyd) (22) and 5-hydroxy-2 -deoxyuridine (5-OHdUrd) (23) that are produced from dehydration reactions of 5,6-dihydroxy-5,6-dihydro-2 -deoxycytidine (20) and 5,6-dihydroxy-5,6-dihydro-2 -deoxyuridine (21), respectively. MQ-photosen-sitized oxidation of dCyd also results in the formation of six minor nucleoside photoproducts, which include the two trans diastereomers of AT-(2-de-oxy-/j-D-eryf/iro-pentofuranosyl)-l-carbamoyl-4 5-dihydroxy-imidazolidin-2-one, h/1-(2-deoxy-J8-D-crythro-pentofuranosyl)-N4-ureidocarboxylic acid and the a and [5 anomers of N-(2-deoxy-D-eryfhro-pentosyl)-biuret [32, 53]. In contrast, formation of the latter compounds predominates in OH radical-mediated oxidation of the pyrimidine ring of dCyd, which involves preferential addition of OH radicals at C-5 followed by intramolecular cyclization of 6-hydroperoxy-5-hydroxy-5,6-dihydro-2 -deoxycytidine and subsequent generation of the 4,6-endoperoxides [53]. 

Fig. 8 Long range charge transport between dppz complexes of Ru(III) and an artificial base, methyl indole, in DNA. The methyl indole is paired opposite cytosine and separated from the intercalating oxidant by distances up to 37 A. In all assemblies, the rate constant for methyl indole formation was found to be coincident with the diffusion-controlled generation of Ru(III) (> 107 s )> indicating that charge transport is not rate limiting over this distance regime...

The hydrazide derivative of AMCA can be used to modify aldehyde- or ketone-containing molecules, including cytosine residues using the bisulfite activation procedure described in Chapter 27, Section 2.1. AMCA-hydrazide reacts with these target groups to form hydrazone bonds (Figure 9.26). Carbohydrates and glycoconjugates can be labeled specifically at their polysaccharide portion if the required aldehydes are first formed by periodate oxidation or another such method (Chapter 1, Section 4.4). 

Biotin-hydrazide has been used to biotinylate antibodies at their oxidized carbohydrate residues (O Shanessy et al., 1984, 1987 O Shanessy and Quarles, 1985 Hoffman and O Shannessy, 1988), to modify the low-density lipoprotein (LDL) receptor (Wade et al., 1985), to biotinylate nerve growth factor (NGF) (Rosenberg et al., 1986), and to modify cytosine groups in oligonucleotides to produce probes suitable for hybridization assays (Reisfeld et al., 1987) (Chapter 27, Section 2.3). 

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],... 

Another example relates to OH -aided one-electron oxidation of cytosine. With cytosine, the OH reaction proceeds by addition to C(5), a process that has a selectivity of 90% [24]. The 5-hydroxy-6-yl radical is an excellent reductant, and the same is true for the ionized 6-yl radical formed by deprotonation from N(l). This radical anion now contaim sufficient electron density to eliminate the OH group at C(5) as OH". The result is the cytosine-l-yl radical which is oxidizing, probably due to appreciable spin density at the hetero atoms N(l) and... 

In addition to the protein and low-molecular-weight thiols that react with PAN, there are several other reactive biochemicals. Reduced nicotinamide derivatives are susceptible to oxidation by PAN (at 72 ppm for 1-5 min), whereas the oxidized forms are resistant. The capability of PAN to oxidize these compounds rapidly dissipates in aqueous solution, with a half-life of 4-10 min, depending on pH. The oxidation products appear to be the biologically active forms of the nicotinamide derivatives. Purines and pyrimidines react with PAN (at 1,000 ppm for 30-120 min). The order of sensitivity is thymine, guanine, uracil, cytosine, and adenine. Their reactions were studied at relatively low pH and at high PAN concentration and are probably not of biologic significance. 

Utilising a reversion assay in Salmonella enterica, Prieto et al reported an increased frequency of point mutations following bile-salt exposure. Mutations were predominantly nucleotide substitutions (GC to AT transitions) and -1 frameshift mutations.The frameshifts were dependent on SOS induction and linked to the activity of DinB polymerase (Pol IV). The authors proposed that the GC to AT transitions stimulated by bile, could have arisen from oxidative processes giving rise to oxidised cytosine residues. Consistent with this hypothesis, the authors demonstrated that strains of S. enterica-lacking enzymes required for base-excision repair (endonuclease III and exonuclease IV) and the removal of oxidised bases, demonstrated increased bile-acid sensitivity compared with competent strains. In another study using E. coli, resistance to the DNA-damaging effects of bile was associated with Dam-directed mismatch repair, a pathway also involved with the repair of oxidative DNA lesions. ... 

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