Pyridyl-Substituted Corrole Isomers: Synthesis and their Regulation to G-quadruplex Structures
Pyridyl-Substituted Corrole Isomers: Synthesis and their Regulation to G-quadruplex Structures
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吡啶基取代的咔咯异构体：合成及其对 G-四链体结构的调控
DOI：
10.1002/asia.200900270
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发表时间：
2010-01-01
影响因子：
4.1
通讯作者：
Zhou, Xiang
中科院分区：
文献类型：
--
作者：
Ma, Heng;Zhang, Ming;Zhou, Xiang
G-quadruplex DNA在设计和开发抗肿瘤药物的潜在治疗靶点中起着重要的作用。由于启动子区或端粒中的不同G-四链体序列可以形成不同的二级结构模式，并显示出多样的生物学功能，因此通过区分不同类型的G-四链体来治疗不同的疾病可能需要不同的G-四链体相互作用剂。我们合成了五种阳离子甲基吡啶类化合物，并利用表面等离子体共振技术比较了它们与不同类型的G-四链体如c-myc、htelo和bcl 2的相互作用。由于端粒G-四链体DNA的重要性，我们采用CD、T-m、PCR-stop（PCR = polymerase chain reaction）和polymerase-stop等方法研究了端粒G-四链体DNA与咔咯异构体相互作用的生物学特性，证明了咔咯具有诱导和稳定端粒G-四链体DNA的能力。这项研究提供了第一个实验的洞察如何选择性可能实现不同的G-四链体由一个单一的一组甲基吡啶并吡咯异构体，可能是潜在的选择性癌症治疗优化。
G-quadruplex DNA plays an important role in the potential therapeutic target for the design and development of anticancer drugs. As various G-quadruplex sequences in the promoter regions or telomeres can form different secondary structural modes and display a diversity of biology functions, variant G-quadruplex interactive agents may be necessary to cure different disease by differentiating variant types of G-quadruplexes. We synthesize five cationic methylpyridylium corroles and compare the interactions of corroles with different types of G-quadruplexes such as cmyc, htelo, and bcl2 by using surface plasmon resonance. Because of the importance of human telomere G-quadruplex DNA, we focus on the biological properties of the interactions between human telomere G-quadruplex DNA and corrole isomers using CD, T-m, PCR-stop (PCR = polymerase chain reaction), and polymerase-stop assay, which demonstrate the excellent ability of the corrole to induce and stabilize the G-quadruplex. This study provides the first experimental insight into how selectivity might be achieved for different G-quadruplexes by a single group of methylpyridylium corrole isomers that may be optimized for potential selective cancer therapy.