Characterization of Hydantoin Products from One-Electron Oxidation of 8-Oxo-7,8-dihydroguanosine in a Nucleoside Model

Use of one-electron oxidants such as Na2IrCl6 to oxidize 8-oxo-7,8-dihydro-2‘-deoxyguanosine (OG) residues in oligodeoxynucleotides was previously shown to lead to predominant formation of a base lesion of mass M − 10 compared to starting material [Duarte et al. (1999) Nucleic Acids Res. 27, 596−502...

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Bibliographic Details
Published in:Chemical research in toxicology 2001-07, Vol.14 (7), p.927-938
Main Authors: Luo, Wenchen, Muller, James G, Rachlin, Elliot M, Burrows, Cynthia J
Format: Article
Language:English
Subjects:
8-oxo-7,8-dihydro-2'-deoxyguanosine
Allantoin - analogs & derivatives
Allantoin - analysis
Allantoin - chemistry
Allantoin - metabolism
DNA - metabolism
Guanidines - analysis
Guanidines - chemistry
Guanidines - metabolism
Guanosine - analogs & derivatives
Guanosine - analysis
Guanosine - chemistry
hydantoin
Hydantoins - analysis
Hydantoins - chemistry
Hydrogen-Ion Concentration
Isomerism
Isotope Labeling
Magnetic Resonance Spectroscopy
Models, Molecular
Oxidation-Reduction
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Summary:Use of one-electron oxidants such as Na2IrCl6 to oxidize 8-oxo-7,8-dihydro-2‘-deoxyguanosine (OG) residues in oligodeoxynucleotides was previously shown to lead to predominant formation of a base lesion of mass M − 10 compared to starting material [Duarte et al. (1999) Nucleic Acids Res. 27, 596−502]. To thoroughly characterize the structure of this lesion, the oxidation of the nucleoside 9-N-(2‘,3‘,5‘-tri-O-acetyl-β-d-erythro-pentanosyl)-8-oxo-7,8-dihydroguanine with one-electron oxidants at pH 2−4 was used as a model for duplex DNA oxidation of OG residues. 1H NMR and H,H COSY NMR studies in CD3OD along with LC-ESI-MS/MS fragmentation analysis are consistent with the assignment of the M − 10 species as a mixture of two pH-dependent equilibrating isomers, a guanidinohydantoin (Gh) and an iminoallantoin (Ia) nucleoside, both present as mixtures of epimers at the C5 position of the hydantoin ring, i.e., four total isomers are formed. The Gh/Ia mixture is formed from hydration and decarboxylation of the initially formed intermediate 5-hydroxy-8-oxo-7,8-dihydroguanosine, a species that is also produced by four-electron oxidation (e.g., singlet oxygen) of guanosine. The product mixture can be further oxidized to a species designated Iaox, a hydrolytically unstable material at pH 7 that has been characterized by ESI-MS and 1H NMR. Competition studies with 8-oxo-7,8-dihydroadenosine placed the redox potential of Gh/Ia at about 1.0 V vs NHE. These studies provide important information concerning the structures of lesions obtained when OG, a “hot spot” for oxidative damage, serves as a “hole trap” in long-range electron-transfer studies.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx010072j