Hole transfer in DNA and photosensitized DNA damage: Importance of adenine oxidation
Hole transfer in DNA and photosensitized DNA damage: Importance of adenine oxidation
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DOI：
10.1021/jp0661847
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发表时间：
2007-03-08
影响因子：
3.3
通讯作者：
Majima, Tetsuro
中科院分区：
文献类型：
--
作者：
Kawai, Kiyohiko;Osakada, Yasuko;Majima, Tetsuro
研究了两种著名的 DNA 损伤光敏剂 (Sens) 萘二甲酰亚胺 (NI) 和萘二酰亚胺 (NDI) 的光敏 DNA 损伤反应，它们具有相似的光物理性质，但氧化还原性质不同。合成了 NI 和 NDI 衍生物（NIN、NDIN），它们具有阳离子侧链，并且由于 DNA 的带负电荷的磷酸基团与阳离子基团之间的良好静电相互作用而与 DNA 静电结合；以及 NIP 和 NDIP，它们具有磷酸基团并且不与 DNA 结合。 NIN和NDIN可以通过其单重激发态氧化A和G，NDIP通过其三重激发态氧化A和G，而NIP仅氧化G。在Sens存在的情况下，对多个DNA序列进行了激光闪光光解动力学研究和光敏DNA损伤的定量HPLC分析。NIN、NDIN和NDIP氧化A，在光照射时引起显着的DNA损伤，并且DNA损伤产量随着连续照射时间的延长而增加。伸展一下。相比之下，仅氧化 G 的 NIP 仅对 DNA 造成中度损伤，并且对连续的 A 序列没有表现出偏好。这些结果清楚地证明了 A 氧化的重要性，尤其是在连续的 A 序列中，它会触发 A 之间的快速空穴转移。
Photosensitized DNA damage reactions were investigated for two well-known DNA-damaging photosensitizers (Sens), naphthalimide (NI) and napthaldiimide (NDI), which have similar photophysical properties but differ in their redox properties. NI and NDI derivatives (NIN, NDIN), which have cationic side chains and electrostatically binding to DNA due to favorable electrostatic interactions between the negatively charged phosphate groups of DNA and cationic groups, and NIP and NDIP, which possess phosphate groups and do not bind to DNA, were synthesized. NIN and NDIN can oxidize A and G via their singlet excited state, and NDIP oxidizes A and G via its triplet excited state, whereas NIP oxidizes only G. A combination of laser flash photolysis kinetic studies and quantitative HPLC analyses of photosensitized DNA damage was performed for several DNA sequences in the presence of Sens. NIN, NDIN, and NDIP, which oxidizes A, caused significant DNA damage upon photoirradiation, and DNA damage yield increased with the length of the consecutive A stretch. In contrast, NIP, which oxidizes only G, caused only moderate damage to DNA and showed no preference for the consecutive A sequences. These results clearly demonstrate the importance of A-oxidation, especially in consecutive A sequences, which triggers the rapid hole transfer between A's.