Solution Structure of an Intramolecular (3 + 1) Human Telomeric G-Quadruplex Bound to a Telomestatin Derivative

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• 作者：Wan Jun Chung ; Brahim Heddi ; Masayuki Tera ; Keisuke Iida ; Kazuo Nagasawa ; Anh Tu芒n Phan
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：September 11, 2013
• 年：2013
• 卷：135
• 期：36
• 页码：13495-13501
• 全文大小：358K
• 年卷期：v.135,no.36(September 11, 2013)
• ISSN：1520-5126

文摘

Guanine-rich human telomeric DNA can adopt secondary structures known as G-quadruplexes, which can be targeted by small molecules to achieve anticancer effects. So far, the structural information on complexes between human telomeric DNA and ligands is limited to the parallel G-quadruplex conformation, despite the high structural polymorphism of human telomeric G-quadruplexes. No structure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here we present the first high-resolution structure of the complex between an intramolecular (3 + 1) human telomeric G-quadruplex and a telomestatin derivative, the macrocyclic hexaoxazole L2H2-6M(2)OTD. This compound is observed to interact with the G-quadruplex through 蟺-stacking and electrostatic interactions. This structural information provides a platform for the design of topology-specific G-quadruplex-targeting compounds and is valuable for the development of new potent anticancer drugs.