Long-range oxidation of guanine by Ru(III) in duplex DNA
Long-range oxidation of guanine by Ru(III) in duplex DNA
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DOI：
10.1016/s1074-5521(97)90129-0
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发表时间：
1997-05-01
影响因子：
--
通讯作者：
Barton, JK
中科院分区：
文献类型：
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作者：
Arkin, MR;Stemp, EDA;Barton, JK
背景：理论和实验研究表明，DNA 中的 5'-GG-3' 序列是氧化损伤的“热点”，但很少有研究明确解决 DNA 氧化损伤是否可能通过长程电荷迁移从远处产生。为此，我们制备了系留钌 (Ru)-寡核苷酸双链体，并使用快速猝灭策略来证明通过 DNA 双螺旋的长程电荷传输。结果：含有系留 Ru(II) 嵌入剂的 DNA 组装体已合成。 Ru(III) 在存在外部结合的电子转移猝灭剂的情况下原位生成，选择性地促进 5'-GG-3' 双峰的 5'-G 处的碱基损伤，该双峰位于距氧化剂结合位点 37 埃的位置。在没有鸟嘌呤双联体的情况下，链中所有鸟嘌呤碱基都会发生氧化损伤。在 G.A 错配中也观察到了鸟嘌呤的长程氧化损伤，但在 G.T 错配中则没有。结论：本研究在实验、应用和细胞内可能的反应方面扩展了长程电子转移化学的范围。在这里，我们证明了使用基态氧化剂在大约 37 埃的距离内以高量子产率发生的 DNA 氧化损伤。这些结果表明自由基在 DNA 双链体上达到最低能量位点的平衡。此外，这种电荷迁移对 DNA 碱基对形成的中间 pi 堆栈敏感，因此可能有助于检测错配。
Background: Theoretical and experimental studies have demonstrated that 5'-GG-3' sequences in DNA are 'hot spots' for oxidative damage, but few studies have definitively addressed whether oxidative damage to DNA may arise from a distance via long-range charge migration. Towards this end, we have prepared tethered ruthenium(Ru)-oligonucleotide duplexes and used a flash-quench strategy to demonstrate long-range charge transport through the DNA double helix.Results: DNA assemblies containing a tethered Ru(II) intercalator have been synthesized. Ru(III), generated in situ in the presence of externally bound electron-transfer quenchers, promotes base damage selectively at the 5'-G of a 5'-GG-3' doublet located similar to 37 Angstrom from the binding site of the oxidant. In the absence of a guanine doublet, oxidative damage occurs equally at all guanine bases in the strand. Oxidative damage is also observed at long range for guanine in a G.A mismatch but not in a G.T mismatch.Conclusions: The present study expands the scope of long-range electron-transfer chemistry in terms of experiments, applications, and possible reactions within the cell. Here we demonstrate oxidative damage to DNA occurring with a high quantum yield over a distance of similar to 37 Angstrom using a ground-state oxidant, These results point to the equilibration of the radical across the DNA duplex to the sites of lowest energy. In addition, this charge migration is sensitive to the intervening pi-stack formed by DNA base pairs and hence may be useful for the detection of mismatches.