Characterization of hydantoin products from one-electron oxidation of 8-oxo-7,8-dihydroguanosine in a nucleoside model
Characterization of hydantoin products from one-electron oxidation of 8-oxo-7,8-dihydroguanosine in a nucleoside model
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DOI：
10.1021/tx010072j
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发表时间：
2001-07-01
影响因子：
4.1
通讯作者：
Burrows, CJ
中科院分区：
文献类型：
--
作者：
Luo, WC;Muller, JG;Burrows, CJ
使用单电子氧化剂（如Na2IrCl6）氧化寡脱氧核苷酸中的8-氧-7,8-二氢-2 ' -脱氧鸟苷（OG）残基，与起始物质相比，先前的研究表明，主要形成质量为M - 10的碱基损伤[Duarte et al.（1999）核酸研究，27,596-502]。为了彻底表征这种病变的结构，我们使用单电子氧化剂在pH 2-4下氧化核苷9-N-（2 ',3 ',5 ' -三-o -乙酰- β -d -红戊烷基）-8-氧-7,8-二氢鸟嘌呤作为OG残基双链DNA氧化的模型。CD3OD的H-1 NMR和H，H COSY NMR研究以及LC-ESI-MS/MS片段分析与M - 10的分配是一致的，M - 10是两个ph依赖的平衡异构体的混合物，一个鸟嘌呤-乙酰胆碱（Gh）和一个亚胺尿囊素（Ia）核苷，两者都是在乙酰胆碱环C5位置的外显体混合物，即形成了四个共异构体。Gh/Ia混合物是由最初形成的中间产物5-羟基-8-氧-7,8-二氢鸟苷的水合作用和脱羧作用形成的，鸟苷也可以通过鸟苷的四电子氧化（例如单线态氧）产生。产物混合物可以进一步氧化为一种名为Ia（ox）的物质，这是一种在pH为7时水解不稳定的物质，已通过ESI-MS和H-1 NMR进行了表征。与8-氧-7,8-二氢腺苷的竞争研究表明，Gh/Ia的氧化还原电位约为1.0 V vs NHE。当氧化损伤的“热点”OG在远程电子转移研究中充当“空穴陷阱”时，这些研究提供了关于损伤结构的重要信息。
Use of one-electron oxidants such as Na2IrCl6 to oxidize 8-oxo-7,8-dihydro-2 ' -deoxyguanosine (OG) residues in oligodeoxynucleotides was previously shown to lead to predominant formation of a base lesion of mass M - 10 compared to starting material [Duarte et al. (1999) Nucleic Acids Res. 27, 596-502]. To thoroughly characterize the structure of this lesion, the oxidation of the nucleoside 9-N-(2 ' ,3 ' ,5 ' -tri-O-acetyl-beta -D-erythro-pentanosyl)-8-oxo-7,8-dihydroguanine with one-electron oxidants at pH 2-4 was used as a model for duplex DNA oxidation of OG residues. H-1 NMR and H,H COSY NMR studies in CD3OD along with LC-ESI-MS/MS fragmentation analysis are consistent with the assignment of the M - 10 species as a mixture of two pH-dependent equilibrating isomers, a guanidinohydantoin (Gh) and an iminoallantoin (Ia) nucleoside, both present as mixtures of epimers at the C5 position of the hydantoin ring, i.e., four total isomers are formed. The Gh/Ia mixture is formed from hydration and decarboxylation of the initially formed intermediate 5-hydroxy-8-oxo-7,8-dihydroguanosine, a species that is also produced by four-electron oxidation (e.g., singlet oxygen) of guanosine. The product mixture can be further oxidized to a species designated Ia(ox), a hydrolytically unstable material at pH 7 that has been characterized by ESI-MS and H-1 NMR. Competition studies with 8-oxo-7,8-dihydroadenosine placed the redox potential of Gh/Ia at about 1.0 V vs NHE. These studies provide important information concerning the structures of lesions obtained when OG, a "hot spot" for oxidative damage, serves as a "hole trap" in long-range electron-transfer studies.