Peroxynitrite reacts with 8-nitropurines to yield 8-oxopurines.
Peroxynitrite reacts with 8-nitropurines to yield 8-oxopurines.
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过氧亚硝酸盐与 8-硝基嘌呤反应生成 8-氧代嘌呤。
DOI：
10.1021/tx010093d
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发表时间：
2002
影响因子：
4.1
通讯作者：
Tannenbaum,StevenR
中科院分区：
文献类型：
--
作者：
Lee,JosephM;Niles,JacquinC;Wishnok,JohnS;Tannenbaum,StevenR
过氧亚硝酸盐与 2'-脱氧鸟苷反应产生几种主要产物，包括 8-oxo-2'-脱氧鸟苷 (8-oxodG) 和 8-硝基鸟嘌呤 (8-硝基Gua)。虽然之前已经对 8-oxodG 与过亚硝酸盐反应过程中形成的末端产物进行了表征，但由 8-硝基Gua 形成的末端产物尚未进行表征。为了鉴定这些产物，使用 9-乙基-8-硝基黄嘌呤作为 8-硝基瓜的模型，因为前者可以很容易地以高产率合成，并且有利于所得产物的反相 HPLC 分离。使用该模型底物，过氧亚硝酸盐反应过程中形成的产物被鉴定为草酸、5-亚氨基咪唑烷-2,4-二酮,III、[N-硝基-N'-[2,4-二氧代咪唑烷-5-亚基]-脲,V、脱氢尿囊素、对羟基苯甲酸、氰尿酸和尿酸的乙基衍生物。根据之前对 8-oxodG 的研究，这些产物被认为是由过亚硝酸盐介导的尿酸氧化产生的产物。此外，反应混合物中尿酸的存在使我们提出了一个模型，其中8-硝基嘌呤首先转化为8-氧代嘌呤，8-氧代嘌呤进一步被过氧亚硝酸盐氧化，得到观察到的最终产物。我们还提供了证据，表明过氧亚硝酸根阴离子作为亲核试剂，可能是 8-硝基嘌呤最初转化为 8-氧代嘌呤的原因，而羟基自由基或氧化过程不太可能解释这种转化。
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.