Study of the Mode and Efficiency of DNA Binding in the Damage Induced by Photoactivated Water Soluble Porphyrins
Study of the Mode and Efficiency of DNA Binding in the Damage Induced by Photoactivated Water Soluble Porphyrins
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DOI：
10.1111/php.12088
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发表时间：
2013-09-01
影响因子：
3.3
通讯作者：
Epe, Bernd
中科院分区：
文献类型：
--
作者：
Karunakaran, Suneesh C.;Ramaiah, Danaboyina;Epe, Bernd
我们用多种光谱技术和修复核酸内切酶研究了中性水溶性卟啉衍生物5，10，15，20-tetrakis(2，4，6-trihydroxyphenyl)porphyrin(TTHPP)及其锌衍生物5，10，15，20-tetrakis(2，4，6-trihydroxyphenyl)porphyrinato锌(II)在可见光照射下的结合作用和体外光激活的DNA损伤。通过紫外-可见吸收光谱、发射光谱、圆二色光谱和粘度的变化表明，这些卟啉衍生物通过沟槽结合作用对DNA具有很高的亲和力。有趣的是，与其金属衍生物和著名的光敏剂血卟啉相比，游离碱衍生物TTHPP产生了有效的单线态氧介导的DNA损伤，对甲酰胺嘧啶-DNA糖基酶(FPG蛋白)敏感。这些结果为DNA结合方式以及与DNA的相互作用程度在中性卟啉诱导的光激活DNA损伤效率中的作用提供了直接证据，中性卟啉被认为是光动力治疗应用的理想候选者。
We have investigated the DNA binding interactions and in vitro photoactivated DNA damage induced by a neutral water soluble porphyrin derivative 5,10,15,20-tetrakis(2,4,6-trihydroxyphenyl)porphyrin (TTHPP) and its zinc derivative 5,10,15,20-tetrakis(2,4,6-trihydroxyphenyl)porphyrinato zinc(II) (Zn-TTHPP) upon visible light irradiation through various spectroscopic techniques and employing repair endonucleases. These porphyrin derivatives exhibited high affinity toward DNA through groove binding interactions as evidenced through the UV-vis absorption, emission, circular dichroism spectral and viscosity changes. Interestingly, the free base porphyrin derivative, TTHPP generated efficient singlet oxygen mediated DNA damage sensitive to formamidopyrimidine-DNA glycosylase (Fpg protein), when compared with its metal derivative and to the well-known photosensitizer, hematoporphyrin. These results provide direct evidence for the role of DNA binding mode as well as extent of interactions with DNA in the efficiency of photoactivated DNA damage induced by the neutral porphyrins, which are believed to be the ideal candidates for photodynamic therapeutic applications.