G-四链体DNA结合剂研究进展  

Progress in the Study of G-Quadruplex DNA Binders

作　　者：郝润[1] 刘雅萌[1] 张淑芬[1] 罗云敬[1] 钟儒刚[1] 

机构地区：[1]北京工业大学生命科学与生物工程学院,北京100124

出　　处：《现代生物医学进展》2014年第13期2560-2562,共3页Progress in Modern Biomedicine

基　　金：北京市教委科技计划重点项目(KZ201110005003)

摘　　要：富含鸟嘌呤的单链DNA序列可以缠绕折叠形成G-四链体结构。人类基因组中有36,000个以上的DNA序列有潜力生成G-四链体,如端粒末端重复序列,以及c-myc、c-kit、bcl-2等原癌基因启动子区域。G-四链体是由四个鸟嘌呤之间通过Hoogsteen氢键形成G-四分体,相邻的G-四分体再通过π-π堆积作用,由糖-磷酸骨架相连而成。G-四链体DNA的形成有着重要的生物学意义,它和相关基因表达水平密切相关,诱导和稳定G-四链体结构就有可能抑制癌基因的转录和表达,引起肿瘤细胞生物学功能的紊乱,从而抑制肿瘤细胞的增殖。G-四链体结构作为新的抗肿瘤药物靶点引起了科学家的广泛关注,能够稳定G-四链体结构的配体包括二酰胺蒽醌类、苝类、阳离子卟啉类、金属配合物和天然产物等。本文对近年来以G-四链体为靶点的配体的研究进行了综述。Guanine-rich DNA sequences can flod G-quadruplex structure. More than 36,000 DNA sequences in the human genome has the potential to form G-quadruplex structure, such as telomeric chromosomal terminals and c-myc, c-kit, bcl-2 oncogene promoter region. G-quadruplex structure is composed of stacked guanine tetrads which is assembled via Hoogsteen hydrogen-bonding in a coplanar arrangement. The formation of DNA G-quadruplex have important biological significance and it is related to the level of gene expression. The induction and stabilization of G-quadruplex structure can lead to the biology disorder of tumor cell, thereby inhibiting the proliferation of tumor cell. G-quadruplex structure, as a new anticancer drug target, has caused much attention. The ligands which can stabilize the G-quadruplex structure include diamide anthraquinone, perylene, cationic porphyrins, metal complexes and natural products. This article briefly describes the formation and biological significance of G-quadruplex, also current developments in G-quadruplex targeted ligands were reviewed.

关 键 词：G-四链体 端粒 原癌基因 抗肿瘤药物 

分 类 号：R730.53[医药卫生—肿瘤]