原癌基因c-myc启动区G-四链体结构及靶向小分子配体  

Structure of G-Quadruplex in the Oncogene c-myc Promoter and Small Ligands Targeting the G-Quadruplex

作　　者：田明月[1,2] 张秀凤[2] 潘然[2] 赵长琦[1] 唐亚林[2] 

机构地区：[1]北京师范大学生命科学学院基因工程药物及生物技术北京市重点实验室,北京100875 [2]中国科学院化学研究所分子动态与稳态国家重点实验室,北京100190

出　　处：《化学进展》2010年第5期983-992,共10页Progress in Chemistry

基　　金：中国科学院分子科学中心创新项目(No.CMS-CX200801)资助

摘　　要：随着DNAG-四链体结构的发现和现代分子生物学技术对其与癌症关系的揭示,DNAG-四链体逐渐成为抗肿瘤药物研究的新靶点。c-myc启动区G-四链体由于在细胞生长、增殖、凋亡、衰老及肿瘤形成等过程中的重要作用,成为DNAG-四链体中最受关注的序列之一。本文旨在对c-myc启动区G-四链体的结构及靶向c-mycG-四链体的小分子配体的研究进展进行综述。首先,介绍c-mycG-四链体的生物学意义;其次,对几种常用的c-mycG-四链体的结构进行解析;最后,对以c-myc为靶点的小分子配体的研究进展及其与G-四链体的作用模式进行综述,并对目前以c-mycG-四链体为靶点、已经走向临床实验的CX-3543的开发与作用机制进行介绍。The revealing of the relationship between the G-quadruplex and cancer by modern molecular biology techniques provides a new opportunity to the anti-cancer drugs research. Because of the important effect on cellular proliferation and apoptosis, the G-quadruplex in the c-myc promoter has emerged as an attractive target for anti-cancer therapeutic agents. The present article aims to highlight recent advances in the structure of G- quadruplex in the oncogene c-myc promoter and small ligands targeting the G-quadruplex. Firstly, the biological significance of c-myc G-quadruplex is introduced. Secondly, the structures of several c-myc G-quadruplexs are analyzed. Finally, the development of the small ligands targeting c-myc G-quadruplex is introduced, and the mechanism of the quadruplex-related drug candidate CX-3543 which has entered phase I clinical trial has been explored.

关 键 词：原癌基因C-MYC G-四链体 NMR小分子配体 

分 类 号：Q523[生物学—生物化学] Q74