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首页> 外文期刊>RSC Advances >A water-soluble cationic porphyrin showing pH-dependent G-quadruplex recognition specificity and DNA photocleavage activity
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A water-soluble cationic porphyrin showing pH-dependent G-quadruplex recognition specificity and DNA photocleavage activity

机译：水溶性阳离子卟啉，显示pH依赖的G-四链体识别特异性和DNA光裂解活性

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摘要

G-quadruplex ligands lacking recognition specificity against duplex DNA are considered to be unsatisfactory due to non-specific cytotoxicity. However, a G-quadruplex ligand, which can interact with duplex DNA under acidic conditions but not under neutral conditions, may be highly desirable for cancer therapy because it can kill cancer cells with high efficiency, with very few side effects on healthy cells. Herein, a new water-soluble cationic porphyrin derivative 5,10,15,20-tetra-{4-[2-(1-methyl-1-piperidinyl)ethoxy]phenyl}porphyrin (i-TMPipEOPP) was synthesized and characterized, and its interactions with G-quadruplex and duplex DNA were compared using ultraviolet visible absorption, fluorescence, circular dichroism and gel electrophoresis assays. The results show that i-TMPipEOPP has pH-dependent G-quadruplex recognition specificity. That is, it can interact with both G-quadruplex and duplex DNA under acidic conditions, but can only interact with G-quadruplex under neutral conditions. Because of the synergy between p-p stacking and electrostatic interactions, i-TMPipEOPP interacts with G-quadruplex with higher binding affinity under acidic conditions than under neutral conditions in which only p-p stacking interactions occur. More interestingly, i-TMPipEOPP can mediate pH-dependent DNA photocleavage of duplex DNA and shows pH-dependent phototoxicity to cells. These findings suggest that i-TMPipEOPP may be developed as a promising photodynamic therapy drug showing higher cytotoxicity towards acidic tumor cells than neutral healthy cells.
机译：缺乏对双链体DNA的识别特异性的G-四链体配体由于非特异性的细胞毒性而不能令人满意。然而，在酸性条件下但在中性条件下不能与双链体DNA相互作用的G-四链体配体对于癌症治疗可能是非常理想的，因为它可以高效杀死癌细胞，而对健康细胞的副作用却很小。本文合成了一种新型的水溶性阳离子卟啉衍生物5,10,15,20-四-{4- [2-（2-（1-甲基-1-哌啶基）乙氧基]苯基]苯基}卟啉（i-TMPipEOPP），并对其进行了表征，并利用紫外可见吸收，荧光，圆二色性和凝胶电泳法比较了其与G-四链体和双链体DNA的相互作用。结果表明，i-TMPipEOPP具有pH依赖性的G-四链体识别特异性。即，它可以在酸性条件下与G-四链体和双链体DNA相互作用，但只能在中性条件下与G-四链体相互作用。由于p-p堆积和静电相互作用之间的协同作用，i-TMPipEOPP在酸性条件下比仅在p-p堆积相互作用中性条件下以更高的结合亲和力与G-四链体相互作用。更有趣的是，i-TMPipEOPP可以介导双链DNA的pH依赖性DNA光裂解，并显示出pH依赖性对细胞的光毒性。这些发现表明，i-TMPipEOPP可能被开发为一种有前途的光动力疗法药物，与中性健康细胞相比，它对酸性肿瘤细胞具有更高的细胞毒性。

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