DNA photocleavage by porphyrin-polyamine conjugates

DNA photocleavage by porphyrin-polyamine conjugates
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DOI:
10.1016/j.bmc.2008.11.047
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发表时间:
2009-01-15
影响因子:
3.5
通讯作者:
Krausz, Pierre
Krausz, Pierre
中科院分区:
医学3区
文献类型:
--
作者:
Guillaume, Garcia;Sarrazy, Vincent;Krausz, Pierre

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合成了一系列带有两个(顺式或反式)或四个亚精胺或精胺单元的聚胺-卟啉缀合物。我们通过紫外-可见光谱研究了这些阳离子卟啉与小牛胸腺 DNA 的结合,并研究了它们在光存在下切割质粒 DNA 的能力。研究发现 DNA 结合和 DNA 光裂解能力取决于结构特征,如 (a) 卟啉环上侧链的相对位置和 (b) 所连接侧链(亚精胺或精胺)的性质。还研究了单线态氧猝灭剂 (NaN3) 和羟基自由基清除剂(甘露醇)存在下的 DNA 裂解。单线态氧是先前观察到的 DNA 裂解的主要物质。总的来说,这些数据表明多胺-卟啉缀合物可能是有前途的光治疗剂。 (C) 2009 年,爱思唯尔有限公司出版。
A series of polyamine-porphyrin conjugates bearing two (cis or trans position) or four units of spermidine or spermine was synthesized. We studied the binding of these cationic porphyrins to calf thymus DNA by the means of UV-vis spectroscopy and we investigated their ability to cleave plasmid DNA in the presence of light. DNA binding and DNA photocleavage abilities were found to depend on structural characteristics as (a) the relative positions of the side chains on the porphyrin ring and (b) the nature of the attached side chains (spermidine or spermine). DNA cleavage was also studied in the presence of a singlet oxygen quencher (NaN3) and in the presence of a hydroxyl radical scavenger (mannitol). Singlet oxygen was the major species responsible for the cleavage of DNA previously observed. Collectively, these data show that polyamine-porphyrin conjugates could be promising phototherapeutic agents. (C) 2009 Published by Elsevier Ltd.