Synthesis and properties of DNA oligomers containing 2'-deoxynucleoside N-oxide derivatives.
Synthesis and properties of DNA oligomers containing 2'-deoxynucleoside N-oxide derivatives.
复制标题
含有 2-脱氧核苷 N-氧化物衍生物的 DNA 寡聚物的合成和性质。
DOI：
10.1021/jo7021845
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
M. Sekine
中科院分区：
文献类型：
--
作者：
Hirosuke Tsunoda;A. Ohkubo;H. Taguchi;K. Seio;M. Sekine
长期以来，胞嘧啶和腺嘌呤N-氧化物衍生物一直被认为是过氧化氢等过氧化氢对DNA氧化损伤的产物。尽管2‘-脱氧核苷N-氧化物衍生物的合成和性质已经被很好地描述，但关于含有这些N-氧化物碱基的初始形成的DNA低聚物的化学和生化行为的报道很少。在本研究中，我们建立了一种简便的固相合成2‘-脱氧胞苷N-氧化物(DC O)或2’-脱氧腺苷N-氧化物(DA O)的方法，该方法是利用N保护的DNA低聚物的合成后氧化反应，以高选择性的方式合成含有m-CPBA的目标DC或DA位点以外的DNA寡聚核苷酸。在这一策略中，苯甲酰基、邻苯二甲酰基和(4-异丙基苯氧基)乙酰基分别作为碱基保护基团，避免了腺嘌呤、胞嘧啶和鸟嘌呤在未修饰位置的氧化。
Cytosine and adenine N-oxide derivatives have long been known as products resulting from the oxidative damage of DNA by peroxides such as hydrogen peroxide. Although the synthesis and properties of 2'-deoxynucleoside N-oxide derivatives have been well described, little has been reported about the chemical and biochemical behavior of initially formed DNA oligomers containing these N-oxide bases. In this study, we established a convenient method for the solid-phase synthesis of oligodeoxynucleotides incorporating 2'-deoxycytidine N-oxide (dC O) or 2'-deoxyadenosine N-oxide (dA O) by using the postsynthetic oxidation of N-protected DNA oligomers except for the target dC or dA site with m-CPBA in MeOH in a highly selective manner. In this strategy, the benzoyl, phthaloyl, and (4-isopropylphenoxy)acetyl groups proved to serve as base protecting groups to avoid oxidation of adenine, cytosine, and guanine, respectively, at the unmodified sites.