Thymidine oxidation

There appear also to be toxic effects. In animals, nitrous oxide has been shown to inactivate methionine synthetase which prevents the conversion of deoxyuridine to thymidine and thus has the potential for inducing megaloblastic anemia, leukopenia, and teratogenicity (44—46). A variety of epidemiologic surveys suggest positive correlations between exposure to nitrous oxide and spontaneous abortion in dental assistants (47). 

A method has been reported for the quantification of the DNA oxidation products, 8-hydroxy-2 -deoxyguanosine (8-OH-dG), 8-hydroxy-2 -deoxyadenosine (8-OH-dA), 5-hydroxymethyl-2-deoxyuridine (HMDU), thymidine glycol (TG) and 2-hydroxy-2 -deoxyadenosine (2-OH-dA) [37], The HPLC system employed consisted of a 2.0 X 250 mm Cig column and gradient elution from waterimethanol, (94 6) to (10 90) over 28 min, at a flow rate of 200 tilmin ... 

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. 

A polynucleoside with an unnatural polymeric backbone was synthesized by SBP-catalyzed oxidative polymerization of thymidine 5 -p-hydroxyphenylacetate. Chemoenzymafic synthesis of a new class of poly(amino acid), poly(tyrosine) containing no peptide bonds, was achieved by the peroxidase-catalyzed oxidative polymerization of tyrosine ethyl esters, followed by alkaline hydrolysis. Amphiphile higher alkyl ester derivatives were also polymerized in... 

Production of Mucosal Damage 2.3.1.2.1 Cell culture Stimulated neutrophils are known to be cytotoxic to cells in vitro (Dull et al., 1987 Dallegri et al., 1990 Grisham et al., 1990b). Several in vitro systems have been used to demonstrate oxidative damage to intestinal cells. Xanthine/XO increased Cr release and decreased [ H]thymidine uptake by IEC-18 small intestinal epithelial cell monolayers in a dose-dependent manner (Ma et al., 1991). Rat enterocytes show decreased trypan blue exclusion and increased protein release when incubated with neutrophils stimulated... 

Reaction of the tetrazolide of phosphorous acid diester with a S -protected thymidine and subsequent oxidation with iodine yields the corresponding thymidine phosphortriester [961... 

Interestingly, one-electron oxidants partly mimic the effects of OH radicals in their oxidizing reactions with the thymine moiety of nucleosides and DNA. In fact, the main reaction of OH radicals with 1 is addition at C-5 that yields reducing radicals in about 60% yield [34, 38]. The yield of OH radical addition at C-6 is 35% for thymidine (1) whereas the yield of hydrogen abstraction on the methyl group that leads to the formation of 5-methyl-(2 -de-oxyuridylyl) radical (9) is a minor process (5%). Thus, the two major differences in terms of product analysis between the oxidation of dThd by one-electron oxidants and that by the OH radical are the distribution of thymidine 5-hydroxy-6-hydroperoxide diastereomers and the overall percentage of methyl oxidation products. 

Phenylthioethyl has been used as a protecting group for N-3 of thymidine during manipulation of the sugar. It was removed via oxidation to the sulfone <06SL845>. 

Chromium trioxide in pyridine selectively oxidizes the hydroxymethyl groups in thymidine, 2 -deoxyadenosine, 2 -deoxyguano-sine, and 2 -deoxycytidine to carboxyl groups,525 but the partial liberation of the free, heterocyclic bases in the reactions suggested that oxidation at C-3 also occurs to some extent. 

One-carbon units in different oxidation states are required in the pathways producing purines, thymidine, and many other compounds. When a biochemical reaction requires a methyl group (methylation), S-adenos dmethionme (SAM) is generally the methyl donor. If a one-carbon unit in another oxidation state is required (methylene, methenyl, formyl), tetrahydrofolate (THF) typically serves as its donor. 

The Reformatsky type of reaction with Zn(0) was performed in situ and led to somewhat unstable phosphonodiamidite (step a) which was coupled with 5 -DMTr-thymidine to give the intermediate mononucleoside phospho-noamidite (step b). The latter was further coupled with 3 -acetyl-thymidine (step c). Couplings described in steps b and c were activated by tetrazole. The intermediate dinucleoside phosphonite was oxidized with (lS)-(+)-(10-camphorsulphonyl)oxaziridine (step d) or sulfurized with Beaucage reagent. The phosphonoamidites mentioned above were used in the solid-phase chemical synthesis of phosphonoacetate and thiophosphonoacetate oligonucleotides. 

Thymidine-specific depyrimidination of DNA by this and other Ru(lV) 0x0 complexes, e.g. electrocatalytically by [Ru(0)(py)(bpy)2] Vaq. formate buffer was studied and related to their Ru(IV)/Ru(ll) redox potentiis [664]. Oxidation of formate and of formic acid to CO by stoich. aT-[Ru(0)(py)(bpy)2] Vwater was studied kinetically, and a two-electron hydride transfer mechanism proposed [665]. 

The FOX assay applied to a skatole oxidation product isolated by HPLC gave a positive result, supporting the contention that it is skatolyl hydroperoxide (40) . Mixtures of 183 and the eight diastereoisomeric hydroperoxides 184 and 185 derived from thymidine (42), as shown in equation 64, can be separated and detected by RP-HPLC with UVD at 229 nm. Each isomer is determined by applying the FOX assay using a capillary reactor heated at 60 °C to provide sufficient time for total oxidation of the Fe(ll) ions, followed by UVD at 596 mn . A commercial kit based on the FOX assay for hydroperoxide determination in plasma, serum and tissue homogenizates appears in Table 2. 

An almost complete description of both OH radical-mediated and one-electron oxidation reactions of the thymine moiety (3) of DNA and related model compounds is now possible on the basis of detailed studies of the final oxidation products and their radical precursors. Relevant information on the structure and redox properties of transient pyrimidine radicals is available from pulse radiolysis measurements that in most cases have involved the use of the redox titration technique. It may be noted that most of the rate constants implicating the formation and the fate of the latter radicals have been also assessed. This has been completed by the isolation and characterization of the main thymine and thymidine hydroperoxides that arise from the fate of the pyrimidine radicals in aerated aqueous solutions. Information is also available on the formation of thymine hydroperoxides as the result of initial addition of radiation-induced reductive species including H" atom and solvated electron. 

The HPLC-MS/MS method has been recently applied for the measurement of the cis and trans diastereomers of 5,6-dihydroxy-5,6-dihydrothymidine (8), 5-formyl-2 -deoxyuridine (11) and 5-(hydroxymethyl)-2 -deoxyuridine (10) within cellular DNA exposed to ionizing radiation and heavy particles. The two methyl oxidation products 10 and 11 and thymidine glycols 8 (Chart 3) that are produced within the range of 20 to 100 lesions per 10 normal bases and per Gy (Table 3) are likely to be derived from the decomposition of 5-(hydroperoxymethyl)-2 -deoxyuridine (7) and 5-(6)-hydroperoxy-6-(5)-hydroxy-5,6-dihydrothymidine 5 and 6, respectively. 

The 5,6-double bond in activated pyrimidines can participate in thermal [4-1-2] cyclization reactions as demonstrated by the 1,3-dipolar cycloaddition reactions of O-protected thymidine derivatives 483 with the nonstabilized azo-methine ylide 484, which is generated from trimethylamine AT-oxide by reaction with EDA <2002SC1977>. 

Oxidative desulfurization can also be used to prepare pyrimidine derivatives as demonstrated by the reaction of thymidine derivatives 598 with fra r-2-phenylsulfonyl-3-phenyloxaziridine (PSO) 599 at room temperature, where the dethiated derivatives 600 were obtained in very good yield <2004TL6729>. 

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