Photosensitized cleavage of plasmidic DNA by norharmane, a naturally occurring beta-carboline.
Photosensitized cleavage of plasmidic DNA by norharmane, a naturally occurring beta-carboline.
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去甲哈尔滨（一种天然存在的 β-咔啉）对质粒 DNA 进行光敏切割。
DOI：
10.1039/c002235g
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发表时间：
2010
影响因子：
3.2
通讯作者：
F. Cabrerizo
中科院分区：
文献类型：
--
作者：
M. M. Gonzalez;M. Pellon;Matias A Ales;M. Gonzalez;R. Erra;F. Cabrerizo
UV-A辐射（320-400 nm）通过光敏化反应诱导对DNA分子及其组分的损伤。β-咔啉（betaCs）是一种广泛存在于生物系统中的杂环化合物，参与多种生物过程并能够作为光敏剂。研究了UV-A辐射下去甲哈尔烷对水溶液中质粒DNA的光敏作用。研究了pH对反应的影响，并考察了活性氧（ROS）如羟基自由基（HO*）、超氧阴离子（O（2）（*-））和单线态氧（（1）O（2））的参与。观察到光敏DNA弛豫对pH的强烈依赖性。在pH 4.7下进行的实验中，反应程度高于在pH 10.2下进行的实验。正如预期的那样，在生理pH（pH 7.4）下观察到中等程度的反应。活性氧清除剂的动力学研究表明，活性氧与DNA之间的化学反应不是导致DNA损伤的主要途径。因此，产生DNA链断裂的主要机制最可能通过I型机制（电子转移）从去甲哈尔烷的质子化形式（（1）[nHoH（+）]*）的单一激发态（S（1））发生。通过使用去甲哈尔烷的N-甲基衍生物（N-甲基-去甲哈尔烷）获得关于光裂解反应中所涉及的去甲哈尔烷电子激发态的性质的额外信息。
UV-A radiation (320-400 nm) induces damages to the DNA molecule and its components through photosensitized reactions. Beta-carbolines (betaCs), heterocyclic compounds widespread in biological systems, participate in several biological processes and are able to act as photosensitizers. The photosensitization of plasmidic DNA by norharmane in aqueous solution under UV-A radiation was studied. The effect of pH was evaluated and the participation of reactive oxygen species (ROS), such as hydroxyl radical (HO*), superoxide anion (O(2)(*-)) and singlet oxygen ((1)O(2)) was investigated. A strong dependence of the photosensitized DNA relaxation on the pH was observed. The extent of the reaction was shown to be higher in the experiments performed at pH 4.7 than those performed at pH 10.2. As was expected, an intermediate extent of the reaction was observed at physiological pH (pH 7.4). Kinetic studies using ROS scavengers revealed that the chemical reactions between ROS and DNA are not the main pathways responsible for the damage of DNA. Consequently, the predominant mechanism yielding the DNA strand break takes place most probably via a type I mechanism (electron transfer) from the single excited state (S(1)) of the protonated form of norharmane ((1)[nHoH(+)]*). Additional information about the nature of the norharmane electronic excited states involved in the photocleavage reaction was obtained by using the N-methyl derivative of norharmane (N-methyl-norharmane).