College of Chemistry and Molecular Sciences, Wuhan University, Hubei, Wuhan 430072, P.R. China.
Chem Asian J. 2010 Jan 4;5(1):114-22. doi: 10.1002/asia.200900270.
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.
G-四链体 DNA 在设计和开发抗癌药物的潜在治疗靶点中发挥着重要作用。由于启动子区域或端粒中的各种 G-四链体序列可以形成不同的二级结构模式,并显示出多样性的生物学功能,因此可能需要变体 G-四链体相互作用剂来通过区分不同类型的 G-四链体来治疗不同的疾病。我们合成了五个阳离子甲基吡啶卟啉并通过表面等离子体共振比较了卟啉与不同类型的 G-四链体(如 cmyc、htelo 和 bcl2)的相互作用。由于人端粒 G-四链体 DNA 的重要性,我们专注于人端粒 G-四链体 DNA 与卟啉异构体之间相互作用的生物学特性,使用 CD、T(m)、PCR 停止(PCR=聚合酶链反应)和聚合酶停止测定法,证明了卟啉诱导和稳定 G-四链体的优异能力。这项研究提供了第一个实验见解,即通过一组可能针对潜在选择性癌症治疗进行优化的甲基吡啶卟啉异构体如何实现对不同 G-四链体的选择性。