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DNA binding of metallochlorophylls with affinity to cancer cells

金属叶绿素的 DNA 结合对癌细胞具有亲和力

基本信息

批准号：
10440199
负责人：
INOUE Hidenari
金额：
$ 5.18万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10440199/
关键词：
Chlorophyll metallochlorophyll anionic chlorophyll chlorin DNA photosensitizer PDT cancer cells カオチン性クロロフィル

项目摘要

The metallochlorophylls derived from chloropylls in plants serve as a model of the light harvesting center in photosynthetic system and as a photosensitizer of photodynamic therapy of cancer. They are very efficient as photosensitizers of cancer therapy because of their strong absorption in the visible region in which the laser light is useful due to its high penetration ability into the human skin. The accumulation characteristics of water-soluble metallochlorophylls on can er cells and particularly the interaction of metallochlorophylls with DNA should be understood to get some insights into photodynamic therapy at a molecular level. In the present work, a series of water-soluble metallochlorophylls have been synthesized as photosensitizers in the next generation. Their interaction with DNA has been studied by electronic absorption and circular dichroism spectroscopies and by measurements of thermal denaturation temperatures of DNA.The DNA binding of chlorin e_6 and its derivatives is electrostatic and influenced by the kind of the central ions and the macrocyclic structure, although the binding mode is different from that of metalloporphyrins. A new type of amphoteric (zinc(II) pyropheophorbide a)-glucosamide conjugate exhibits a strong interaction with calf thymus DNA, which has not been observed for the cationic metalloporphyrins. A few cationic metallochlorophylls with a trimethylammoniunmethyl group at the 2a position of chlorin e_6 trimethyl ester or pyropheophorbide a methyl ester have been synthesized. Their DNA binding is hardly affected by the kind of the central metal ions or the structure of the macrocycles. In conclusion, the water-soluble metallochlorophylls here synthesized have been demonstrated to outside bind to the double-helix DNA.

植物中由叶绿素衍生的金属叶绿素是光合系统中捕光中心的模型，也是光动力治疗癌症的光敏剂。它们作为癌症治疗的光敏剂是非常有效的，因为它们在可见光区域中的强吸收，其中激光由于其对人皮肤的高穿透能力而有用。了解水溶性金属叶绿素在癌细胞上的积累特性，特别是金属叶绿素与DNA的相互作用，有助于从分子水平上了解光动力学疗法。本工作合成了一系列水溶性金属叶绿素类光敏剂。通过电子吸收光谱、圆二色光谱和DNA热变性温度的测定，研究了它们与DNA的相互作用，发现它们与DNA的结合方式与金属卟啉不同，但都是静电结合，并受中心离子种类和大环结构的影响。一种新型的两性（焦脱镁叶绿酸a锌（II））-葡萄糖酰胺缀合物与小牛胸腺DNA表现出较强的相互作用，这在阳离子金属卟啉中尚未观察到。合成了几种在二氢卟酚e_6三甲酯或焦脱镁叶绿酸a甲酯的2a位上带有三甲基铵甲基的阳离子金属叶绿素。它们与DNA的结合几乎不受中心金属离子的种类和大环结构的影响。总之，本文合成的水溶性金属叶绿素已被证明可以与双螺旋DNA结合。