G-quadruplexes as targets for drug design
G-quadruplexes as targets for drug design
复制标题
DOI：
10.1016/s0163-7258(99)00068-6
复制
发表时间：
2000-03-01
影响因子：
13.5
通讯作者：
Von Hoff, DD
中科院分区：
文献类型：
--
作者：
Hurley, LH;Wheelhouse, RT;Von Hoff, DD
G-四链体是在单价阳离子存在下形成的二级DNA结构家族，其由四链结构组成，其中Hoogsteen碱基配对稳定G-四联体结构。这些结构被认为存在于体内，但缺乏直接的证实证据。能够形成G-四链体结构的富含鸟嘌呤的DNA区域存在于多种染色体区域中，包括DNA的端粒和启动子区域。在这篇综述中，我们描述了三组不同的G-四链体相互作用的化合物的设计和它们与G-四链体DNA的相互作用。使用第一组化合物（蒽醌类），我们描述了实验，提供了一个G-四链体抑制端粒酶所需的概念证明。使用第二组化合物（二萘嵌苯），我们描述了一个G-四链体配体复合物的结构和它的效果的动力学的形成和酶解的四链体。对于第三组化合物（卟啉），我们描述的实验，其相互作用与G-四链体的生物效应。(C)2000 Elsevier Science Inc. All rights reserved.
G-quadruplexes are a family of secondary DNA structures formed in the presence of monovalent cations that consist of four-stranded structures in which Hoogsteen base-pairing stabilizes G-tetrad structures. These structures are proposed to exist in vivo, although direct confirmatory evidence is lacking. Guanine-rich regions of DNA capable of Forming G-quadruplex structures are found in a variety of chromosomal regions, including telomeres and promoter regions of DNA. In this review, we describe the design of three separate groups of G-quadruplex-interactive compounds and their interaction with G-quadruplex DNA. Using the first group of compounds (anthraquinones), we describe experiments that provide the proof of concept that a G-quadruplex is required for inhibition of telomerase. Using the second group of compounds (perylenes), we describe the structure of a G-quadruplex-ligand complex and its effect on the dynamics of formation and enzymatic unwinding of the quadruplex. For the third group of compounds (porphyrins), we describe the experiments that relate the biological effects to their interactions with G-quadruplexes. (C) 2000 Elsevier Science Inc. All rights reserved.