Tsunoda Hirosuke, Ohkubo Akihiro, Taguchi Haruhiko, Seio Kohji, Sekine Mitsuo
Department of Life Science, Tokyo Institute of Technology, CREST, Japan Science and Technology Agency, Yokohama, 226-8501, Japan.
J Org Chem. 2008 Feb 15;73(4):1217-24. doi: 10.1021/jo7021845. Epub 2008 Jan 18.
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.
胞嘧啶和腺嘌呤N-氧化物衍生物长期以来一直被认为是过氧化氢等过氧化物对DNA进行氧化损伤所产生的产物。尽管2'-脱氧核苷N-氧化物衍生物的合成及其性质已有详尽描述，但关于最初形成的含有这些N-氧化物碱基的DNA寡聚物的化学和生化行为的报道却很少。在本研究中，我们建立了一种简便的方法，通过用间氯过氧苯甲酸（m-CPBA）在甲醇中对除目标dC或dA位点外的N-保护DNA寡聚物进行合成后氧化，以高度选择性的方式固相合成掺入2'-脱氧胞苷N-氧化物（dC O）或2'-脱氧腺苷N-氧化物（dA O）的寡脱氧核苷酸。在该策略中，苯甲酰基、邻苯二甲酰基和（4-异丙基苯氧基）乙酰基分别被证明可作为碱基保护基团，以避免未修饰位点的腺嘌呤、胞嘧啶和鸟嘌呤被氧化。
