Title: Peroxynitrite reacts with 8-nitropurines to yield 8-oxopurines.
Authors: Lee, Joseph M; Niles, Jacquin C; Wishnok, John S; Tannenbaum, Steven R
Published In Chem Res Toxicol, (2002 Jan)
Abstract: 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.
PubMed ID: 11800591
MeSH Terms: Chromatography, High Pressure Liquid; DNA Adducts/analysis; DNA Adducts/chemistry*; Deoxyguanosine/analogs & derivatives; Deoxyguanosine/analysis; Deoxyguanosine/chemistry*; Guanine/analogs & derivatives*; Guanine/analysis; Guanine/chemical synthesis; Guanine/chemistry*; Nitrates/chemistry*; Xanthine/analysis; Xanthine/chemistry*; Xanthines