A novel nitroimidazole compound formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-guanosine.
A novel nitroimidazole compound formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-guanosine.
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DOI：
10.1021/ja004296k
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发表时间：
2001-11
影响因子：
15
通讯作者：
J. Niles;J. Wishnok;S. Tannenbaum
中科院分区：
文献类型：
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作者：
J. Niles;J. Wishnok;S. Tannenbaum
过氧亚硝酸盐与2 '，3'，5 '-三-O-乙酰基-鸟苷反应，生成一种新化合物，经鉴定为1-（2，3，5-三-O-乙酰基-β-D-吡喃-戊呋喃糖基）-5-胍基-4-硝基咪唑（6）。使用UV/维斯光谱和ESI-MS的组合实现该表征。另外，通过独立的路线合成1-（β-D-赤型-戊呋喃糖基）-5-胍基-4-硝基咪唑（6a），通过UV/维斯光谱、ESI-MS和（1）H-和（13）C NMR表征，并且显示与脱乙酰化的6相同。该产品在两种极端pH值下的水溶液中极其稳定，并且以显著的产率形成。这些特征表明，这种病变可能是有用的过氧亚硝酸盐诱导的DNA损伤的特异性生物标志物。我们还观察到2 '，3'，5 '-三-O-乙酰基-8-硝基鸟苷（2'，3 '，5'-三-O-乙酰基-8-NO（2）（）Guo）、2-氨基-5-[（2，3，5-三-O-乙酰基-β-D-吡喃戊呋喃糖基）氨基]-4H-咪唑-4-酮（2 '，3'，5 '-三-O-乙酰基-Iz）和2'，3 '，5'-三-O-乙酰基-8-氧代Guo的过氧亚硝酸盐诱导氧化产物的形成。6和2 ′，3 ′，5 ′-三-O-乙酰基-8-NO（2）（）Guo的形成是通过鸟嘌呤自由基的形成机制来合理化的。
Peroxynitrite reacts with 2',3',5'-tri-O-acetyl-guanosine to yield a novel compound identified as 1-(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6). This characterization was achieved using a combination of UV/vis spectroscopy and ESI-MS. Additionally, 1-(beta-D-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6a) was synthesized by an independent route, characterized by UV/vis spectroscopy, ESI-MS, and (1)H- and (13)C NMR, and shown to be identical to deacetylated 6. This product is extremely stable in aqueous solution at both pH extremes and is formed in significant yields. These characteristics suggest that this lesion may be useful as a specific biomarker of peroxynitrite-induced DNA damage. We also observed formation of 2',3',5'-tri-O-acetyl-8-nitroguanosine (2',3',5'-tri-O-acetyl-8-NO(2)()Guo), 2-amino-5-[(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)amino]-4H-imidazol-4-one (2',3',5'-tri-O-acetyl-Iz), and the peroxynitrite-induced oxidation products of 2',3',5'-tri-O-acetyl-8-oxoGuo. The formation of 6 and 2',3',5'-tri-O-acetyl-8-NO(2)()Guo was rationalized by a mechanism invoking formation of the guanine radical.