One-electron oxidation of guanine and 2'-deoxyguanosine by the azide radical in alkaline solutions
8
Citation
0
Reference
10
Related Paper
Citation Trend
Abstract:
The [math] radical specifically oxidizes 2'-deoxyguanosine at its guanylic moiety. The guanylic radical resulting from this one-electron oxidation is followed by a first-order kinetics process. This is distinctively observed in alkaline solutions (pH ≥ 11) where a new transient could be characterized. This transient exhibits spectra that are similar to those observed with guanine. It is suggested that the oxidized nucleoside radical undergoes a monomolecular process to form an oxidized guanine radical.Keywords:
Deoxyguanosine
Moiety
Radical ion
Oxidation of a guanine nucleobase to its radical cation in DNA oligomers causes an increase in the acidity of the N1 imino proton that may lead to its spontaneous transfer to N3 of the paired cytosine. This proton transfer is suspected of playing an important role in long-distance radical cation hopping in DNA and the decisive product-determining role in the reaction of the radical cation with H2O or O2. We prepared and investigated DNA oligomers in which certain deoxycytidines are replaced by 5-fluoro-2'-deoxycytidines (F5dC). The pKa of F5C was determined to be 1.7 units below that of dC, which causes proton transfer from the guanine radical cation to be thermodynamically unfavorable. Photoinitiated one-electron oxidation of the DNA by UV irradiation of a covalently attached anthraquinone derivative introduces a radical cation that hops throughout the oligomer and is trapped selectively at GG steps. The introduction of F5dC does not affect the efficiency of charge hopping, but it significantly reduces the amount of reaction at the GG sites, as revealed by subsequent reaction with formamidopyrimidine glycosylase. These findings suggest that transfer of the guanine radical cation N1 proton to cytosine does not play a significant role in long-range charge transfer, but this process does influence the reactions with H2O and/or O2.
Radical ion
Nucleobase
Cytosine
Hydroxyl radical
Oligomer
Thymine
Cite
Citations (61)
Deoxyguanosine
Deoxyribose
Glycosidic bond
Ribose
Cite
Citations (7)
Deoxyguanosine
8-Hydroxy-2'-deoxyguanosine
Electrochemical gas sensor
Cite
Citations (52)
Phenylnitrenium ion (PhNH(+)) may bind to nucleophiles through nitrogen as well as through C2 or C4 carbons. However, only adducts of the former type have been hitherto reported after its reaction with purine nucleosides. In this study, reactions of N-acetoxyaniline (PhNHOAc), a precursor to PhNH(+), with 2'-deoxyadenosine (dA), 2'-deoxyguanosine (dG), and with DNA in vitro at physiological conditions are described. The reaction of PhNHOAc with dA followed by a hydrolytic deribosylation afforded 8-phenylaminoadenine (C8-PhNHA) together with a smaller amount of N(6)-(4-aminophenyl)adenine (N(6)-4APA). A similar reaction with dG afforded 8-phenylaminoguanine (C8-PhNHG) together with traces of 7-(4-aminophenyl)guanine (N7-4APG). The same adducts were found also in the DNA treated with PhNHOAc, and all of them were identified by comparison of their HPLC retention times and MS(2) spectra with a set of synthesized authentic adenine adducts at C2, C8, N7, and N(6) positions and guanine adducts at C8, N7, and N(2) positions. The newly identified minor adduct, N7-4APG, represents the first proof of arylnitrenium adduction at the N7 position of dG, which is the prominent site of attack by most C-electrophiles.
Deoxyguanosine
Deoxyadenosine
Nucleobase
Cite
Citations (3)
We have studied the kinetics of guanine incorporation into DNA in mouse T-lymphoma (S-49) mutant cells [PNPase (purine-nucleoside phosphorylase)- and HGPRTase (hypoxanthine: guanine phosphoribosyltransferase)-deficient] that are incapable of converting dGuo (deoxyguanosine) to Gua (guanine) ribonucleotides. Of the two possible pathways for an exogenous guanine source to reach DNA, firstly: dGuo→dGMP→dGDP→dGTP and secondly: Gua→GMP→GDP→dGDP→dGTP only the second pathway was found to be functional in providing guanine for DNA replication, although deoxyguanosine readily produced toxic cellular dGTP levels via the first pathway. The functional guanine-nucleotide-precursor pools for DNA are rather small; further, the depletion of the small GMP pool, but not that of GDP, GTP and dGTP, correlated well with the inhibition of DNA synthesis by mycophenolic acid, an IMP dehydrogenase inhibitor. These results support the hypothesis that guanine-nucleotide incorporation into DNA is highly compartmentalized and that a small functional guanine-nucleotide pool, e.g., the GMP pool, may serve a crucial role in limiting the availability of DNA precursor substrate.
Cite
Citations (34)
2-Cyanoethyldiazohydroxide is a likely product of metabolic alpha-hydroxylation of 3-(methylnitrosamino)propionitrile (MNPN). The reaction of 2-(N-carbethoxy-N-nitrosamino)propionitrile, a stable precursor of 2-cyanoethyldiazohydroxide, with deoxyguanosine, catalyzed by porcine liver esterase, was investigated. Two major deoxyguanosine adducts were produced. They were isolated by high-performance liquid chromatography and characterized by their UV spectra, mass spectra, and proton magnetic resonance spectra. On the basis of these spectral data, the structures of the two adducts were assigned as 7-(2-cyanoethyl)guanine and O6-(2-cyanoethyl)deoxyguanosine. The potential of MNPN to cyanoethylate DNA in F344 rats was evaluated by measuring 7-(2-cyanoethyl)guanine and O6-(2-cyanoethyl)guanine in the liver, nasal mucosa, and esophagus. The highest levels were detected in the nasal cavity, which is one of the major target organs for the carcinogenic effects of MNPN.
Propionitrile
Deoxyguanosine
Hydroxylation
DNA adduct
Cite
Citations (21)
Journal Article A novel photoproduct of 2'-deoxyguanosine induced by acetone photosensitization: 8-(2,3,4-trihydroxybutyl)guanine Get access Narain D. Sharma, Narain D. Sharma Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Jeremy, R. Jeremy Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Davies, H. Davies * *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Dennis R. Phillips, Dennis R. Phillips 1Departments of Medicinal Chemistry and Biochemistry, University of UtahSalt Lake City, UT 84112, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar James A. McCloskey James A. McCloskey 1Departments of Medicinal Chemistry and Biochemistry, University of UtahSalt Lake City, UT 84112, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 17, Issue 3, 11 February 1989, Pages 955–967, https://doi.org/10.1093/nar/17.3.955 Published: 11 February 1989 Article history Received: 08 November 1988 Revision received: 03 January 1989 Accepted: 03 January 1989 Published: 11 February 1989
Deoxyguanosine
Cleavage (geology)
Derivative (finance)
Cite
Citations (9)
The [math] radical specifically oxidizes 2'-deoxyguanosine at its guanylic moiety. The guanylic radical resulting from this one-electron oxidation is followed by a first-order kinetics process. This is distinctively observed in alkaline solutions (pH ≥ 11) where a new transient could be characterized. This transient exhibits spectra that are similar to those observed with guanine. It is suggested that the oxidized nucleoside radical undergoes a monomolecular process to form an oxidized guanine radical.
Deoxyguanosine
Moiety
Radical ion
Cite
Citations (8)
A platinum(IV) complex with a high reduction potential, d,l-1,2-diaminocyclohexyltetrachloroplatinum(IV) (PtIV(dach)Cl4), oxidizes guanine in guanosine-5'-monophosphate (GMP), 2'-deoxyguanosine-5'-monophosphate (dGMP), d(GG), and a double-stranded oligonucleotide to 8-oxo-guanine. To the best of our knowledge, this is the first report that provides unambiguous evidence of DNA oxidation by a PtIV complex. This oxidative damage may differentiate the anticancer activity of PtIV complexes from their PtII analogues.
Deoxyguanosine
Guanosine monophosphate
Cite
Citations (35)
The reaction of 3-methyl-1,2,3-oxadiazolinium tosylate 10, a close model for a putative reactive intermediate in the carcinogenic activation of ethanol nitrosamines such as (2-hydroxyethyl)methylnitrosamine 1, with various guanine derivatives, including acycloguanosine 12, deoxyguanosine, deoxyguanosine monophosphate, and cyclic guanosine monophosphate, various DNA oligomers, and calf-thymus DNA has been examined to determine whether this compound methylates and hydroxyethylates guanine residues as proposed. In all of the transformations, 7-(2-(methylnitrosamino)ethyl)guanine (14) is the major product, following acidic hydrolysis, and exceeds the formation of 7-methylguanine by ratios ranging from 4:1 to 48:1, depending upon the guanine bearing substrate. O6-(2-(Methylnitrosamino)ethyl)deoxyguanosine (20) was prepared from the Mitsunobu coupling of 1 and a protected deoxyguanosine derivative. 20 is not produced in the reaction of 10 and deoxyguanosine and decomposes to 1 and guanine upon mild acid treatment, suggesting possible neighboring group participation in its facile hydrolytic cleavage. All of the major products from the reaction of 10 and 12 have been characterized, including the direct alkylation product, 7-(2-(methylnitrosamino)ethyl)acycloguanosine (13), and N2-(2-(methylnitrosamino)ethyl)guanine, which was independently synthesized. Elucidation of the reactions of DNA with 10 and other electrophiles was facilitated by the development of both partial and total enzymatic hydrolysis assays utilizing 32P-5'-labeled DNA oligotetramers containing one of each base type and HPLC with radiometric detection. The partial hydrolysis assay gives information as to the type of base being modified, and the total hydrolysis assay permits a determination of the number of adducts produced for a given base. The assays permit a comparison between reactions where the same type of base adduct could be expected. Comparisons of the reactions of ethylene oxide and 10 using this methodology showed that 10 does not hydroxyethylate guanine in DNA.
Deoxyguanosine
Cite
Citations (17)