The fate of C5′ radicals of purine nucleosides under oxidative conditions
The fate of C5′ radicals of purine nucleosides under oxidative conditions
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DOI：
10.1021/ja800763j
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发表时间：
2008-07-02
影响因子：
15
通讯作者：
Chatgilialoglu, Chryssostomos
中科院分区：
文献类型：
--
作者：
Boussicault, Fabien;Kaloudis, Panagiotis;Chatgilialoglu, Chryssostomos
在有氧条件下影响嘌呤部分C5'自由基反应性的因素不仅在DNA中是未知的，而且在简单核苷中也是未知的。 5',8-环嘌呤损伤是在与氧反应之前C5'自由基对嘌呤部分进行快速攻击的结果。 DNA 修饰中这些众所周知的损伤被溶液中分子氧的存在所抑制。在这里，我们利用γ-放射分解结合产物研究，阐明了氧化条件下三个嘌呤取代的C5'基团（即2'-脱氧腺苷-5'-基、2'-脱氧肌苷-5'-基和2'-脱氧鸟苷-5'-基）的化学性质。通过水合电子 (e(aq)(-)) 与 8-溴-2'-脱氧腺苷和 8-溴-2'-脱氧肌苷反应选择性生成 2'-脱氧腺苷-5'-基和 2'-脱氧肌苷-5'-基自由基，然后自由基从 C8 位置快速转移到 C5' 位。用 Fe(CN)(6)(3-) 捕获这两个 C5' 自由基，以良好的收率得到相应的水合 5'-醛，并将其分离并充分表征。当使用13-266μM范围内的氧浓度（典型的含氧组织）时，水合的5'-醛伴随着5',8-环嘌呤核苷。 5',8-环嘌呤的形成在所有实验中都是相关的，并且产率随着O 2 浓度的降低而增加。还研究了在常氧条件下HO中心点自由基与2'-脱氧腺苷和2'-脱氧鸟苷的反应。发现 C5' 自由基形成的次要路径约为。 10% 通过量化两个实验中的水合 5'-醛。通过脉冲放射分解测定2'-脱氧腺苷-5'-基与半胱氨酸和谷胱甘肽在水中的反应的速率常数在22℃下分别为(2.1+/-0.5)×10(7)和(4.9+/-0.6)×10(7)M-1s(-1)。
The factors that influence the reactivity of C5' radicals in purine moieties under aerobic conditions are unknown not only in DNA, but also in simple nucleosides. 5',8-Cyclopurine lesions are the result of a rapid C5' radical attack to the purine moieties before the reaction with oxygen. These well-known lesions among the DNA modifications were suppressed by the presence of molecular oxygen in solution. Here we elucidate the chemistry of three purine-substituted C5' radicals (i.e., 2'-deoxyadenosin-5'-yl, 2'-deoxyinosin-5'-yl, and 2'-deoxyguanosin-5'-yl) under oxidative conditions using gamma-radiolysis coupled with product studies. 2'-Deoxyadenosin-5'-yl and 2'-deoxyinosin-5'-yl radicals were selectively generated by the reaction of hydrated electrons (e(aq)(-)) with 8-bromo-2'-deoxyadenosine and 8-bromo-2'-deoxyinosine followed by a rapid radical translocation from the C8 to the C5' position. Trapping these two C5' radicals with Fe(CN)(6)(3-) gave corresponding hydrated 5'-aldehydes in good yields that were isolated and fully characterized. When an oxygen concentration in the range of 13-266 mu M (typical oxygenated tissues) is used, the hydrated 5'-aldehyde is accompanied by the 5',8-cyclopurine nucleoside. The formation of 5',8-cyclopurines is relevant in all experiments, and the yields increased with decreasing 02 concentration. The reaction of HO center dot radicals with 2'-deoxyadenosine and 2'-deoxyguanosine under normoxic conditions was also investigated. The minor path of C5' radicals formation was found to be ca. 10% by quantifying the hydrated 5'-aldehyde in both experiments. Rate constants for the reactions of the 2'-deoxyadenosin-5'-yl with cysteine and glutathione in water were determined by pulse radiolysis to be (2.1 +/- 0.5) x 10(7) and (4.9 +/- 0.6) x 10(7) M-1 s(-1) at 22 degrees C, respectively.