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976579 
Journal Article 
Abstract 
Reactions of peroxynitrite with mono-, di-, and tri-methyluric acids studied by liquid chromatography-mass spectrometry and electron spin resonance spectroscopy 
Imaram, W; Gersch, C; Kim, KM; Johnson, RJ; Henderson, GN; Angerhofer, A 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S61-S61 
English 
WOS:000260867900168 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
Recently, we discovered that uric acid reacts with peroxynitrite to give labile intermediates, which are subsequently converted to triuret. Moreover, in the presence of alcohols, these intermediates were trapped as various alkoxy products. We extended our studies to investigate the effect of methyl substituents at various nitrogen positions, on products and radical for mations. In the presence of methanol, the reactions of seven methyluric acids with peroxynitrite were investigated, and the reaction products were separated and identified by LC-MS. to monitor the reactive radical species, ESR spin trapping methods were used to study the same reaction in phosphate buffer pH 7.4. In ESR spin trapping studies using PBN as the spin trap, a six-line ESR spectrum, corresponding to carbon-based radicals, was observed when N-7 was not methylated. No ESR signal obtained when conducted the reaction with uric acid containing a methyl group on N-7 position. the methylation at other positions reduced the amount of radical adducts for med. Based on MS data, all methylurates reacted with peroxynitrite and the extent of the reaction (from 23 % to 100 %) depended on the position and extent of substitution. Most reactions generated uric acid glycol diethers (I), and methyl allantoin-like compounds (II) were also obtained. Our experiments confirm that urate may act as a pro-oxidant under oxidative stress by for ming urate derived radicals. However, some N-7 substituted urate analogues may exhibit more powerful antioxidant properties than urate, because they can deplete peroxynitrite, but they may not generate radical intermediates, which can potentially be pro-oxidative.

*See pdf for images. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008