Peroxynitrite reacts with 8-nitropurines to yield 8-oxopurines.
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.
Lee
Joseph M
JM
Division of Bioengineering and Environmental Health and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Niles
Jacquin C
JC
Wishnok
John S
JS
Tannenbaum
Steven R
SR
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000032:analysis / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D009566:Nitrates / Q000737:chemistry*; D019820:Xanthine / Q000032:analysis / Q000737:chemistry*; D014970:Xanthines
C095838:8-nitroguanine; C449672:9-ethyl-8-nitoxanthine; D018736:DNA Adducts; D009566:Nitrates; D014970:Xanthines; D019820:Xanthine; C039642:peroxynitric acid; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine