Document Detail

Peroxynitrite reacts with 8-nitropurines to yield 8-oxopurines.
MedLine Citation:
PMID:  11800591     Owner:  NLM     Status:  MEDLINE    
Peroxynitrite reacts with 2'-deoxyguanosine to yield several major products, including 8-oxo-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine (8-nitroGua). While the terminal products formed during the reaction of 8-oxodG with peroxynitrite have been previously characterized, those formed from 8-nitroGua have not. To identify these products, 9-ethyl-8-nitroxanthine was used as a model for 8-nitroGua, since the former could be easily synthesized in high yield, and facilitated reversed-phase HPLC separation of the resulting products. Using this model substrate, the products formed during the peroxynitrite reaction were identified as the ethyl derivatives of oxaluric acid, 5-iminoimidazolidin-2,4-dione, III, [N-nitro-N'-[2,4-dioxo-imidazolidine-5-ylidene]-urea, V, dehydroallantoin, parabanic acid, cyanuric acid, and uric acid. Upon the basis of the previous studies with 8-oxodG, these products were recognized as those expected to arise from peroxynitrite-mediated uric acid oxidation. Furthermore, the presence of uric acid in the reaction mixture led us to propose a model in which the 8-nitropurine is first converted to the 8-oxopurine which is further oxidized by peroxynitrite to give the observed final products. We have also provided evidence suggesting that the peroxynitrite anion, acting as a nucleophile, might be responsible for the initial conversion of the 8-nitropurine to the 8-oxopurine and that a hydroxyl radical or oxidative process is less likely to explain this conversion.
Joseph M Lee; Jacquin C Niles; John S Wishnok; Steven R Tannenbaum
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  15     ISSN:  0893-228X     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-21     Completed Date:  2002-03-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7-14     Citation Subset:  IM    
Division of Bioengineering and Environmental Health and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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MeSH Terms
Chromatography, High Pressure Liquid
DNA Adducts / analysis,  chemistry*
Deoxyguanosine / analogs & derivatives,  analysis,  chemistry*
Guanine / analogs & derivatives*,  analysis,  chemical synthesis,  chemistry*
Nitrates / chemistry*
Xanthine / analysis,  chemistry*
Grant Support
Reg. No./Substance:
0/8-nitroguanine; 0/9-ethyl-8-nitoxanthine; 0/DNA Adducts; 0/Nitrates; 0/Xanthines; 26404-66-0/peroxynitric acid; 69-89-6/Xanthine; 73-40-5/Guanine; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 961-07-9/Deoxyguanosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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