Novel products generated from 2′-deoxyguanosine by hypochlorous acid or a myeloperoxidase–H2O2–Cl– system: identification of diimino-imidazole and amino-imidazolone nucleosides

Hypochlorous acid (HOCl), generated by myeloperoxidase from H2O2 and Cl–, plays an important role in host defense and inflammatory tissue injury. We report here the identification of products generated from 2′-deoxyguanosine (dGuo) with HOCl. When 1 mM dGuo and 1 mM HOCl were reacted at pH 7.4 and 3...

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Bibliographic Details
Published in:Nucleic acids research 2002-06, Vol.30 (11), p.2555-2564
Main Authors: Suzuki, Toshinori, Masuda, Mitsuharu, Friesen, Marlin D., Fenet, Bernard, Ohshima, Hiroshi
Format: Article
Language:English
Subjects:
Chlorides - metabolism
Chromatography, High Pressure Liquid
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - chemistry
Deoxyguanosine - metabolism
Half-Life
Hydrogen Peroxide - metabolism
Hydrogen-Ion Concentration
Hypochlorous Acid - metabolism
Imidazoles - metabolism
Kinetics
Magnetic Resonance Spectroscopy
Nicotine - metabolism
Peroxidase - metabolism
Sodium Chloride - metabolism
Spectrometry, Mass, Electrospray Ionization
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Summary:Hypochlorous acid (HOCl), generated by myeloperoxidase from H2O2 and Cl–, plays an important role in host defense and inflammatory tissue injury. We report here the identification of products generated from 2′-deoxyguanosine (dGuo) with HOCl. When 1 mM dGuo and 1 mM HOCl were reacted at pH 7.4 and 37°C for 15 min and the reaction was terminated with N‐acetylcysteine (N-AcCys), two products were generated in addition to 8-chloro-2′-deoxyguanosine (8-Cl-dGuo). One was identified as an amino-imidazolone nucleoside (dIz), a previously reported product of dGuo with other oxidation systems. The other was identified as a novel diimino-imidazole nucleoside, 2,5-diimino-4-[(2-deoxy-β-d-erythro-pentofuranosyl)amino]-2H,5H-imidazole (dDiz) by spectrometric measurements. The yields were 1.4% dDiz, 0.6% dIz and 2.4% 8-Cl-dGuo, with 61.5% unreacted dGuo. Precursors of dDiz and dIz containing a chlorine atom were found in the reaction solution in the absence of termination by N-AcCys. dDiz, dIz and 8-Cl-dGuo were also formed from the reaction of dGuo with myeloperoxidase in the presence of H2O2 and Cl– under mildly acidic conditions. These results imply that dDiz and dIz are generated from dGuo via chlorination by electrophilic attack of HOCl and subsequent dechlorination by N-AcCys. These products may play a role in cytotoxic and/or genotoxic effects of HOCl.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/30.11.2555