靶向G-四链体的小分子配体在癌症治疗中应用的研究进展  

Research Progresses in Small Molecule G-Quadruplex-Binding Ligands for Applications of Cancer Therapies

作　　者：易卓云 王欣雨 张妍[1] 苏敏 隋广超 赵博 史金铭[1] Yi Zhuoyun;Wang Xinyu;Zhang Yan;Su Min;Sui Guangchao;Zhao Bo;Shi Jinming(College of Life Science,Northeast Forestry University,Harbin,150040)

机构地区：[1]东北林业大学生命科学学院,哈尔滨150040

出　　处：《化学通报》2021年第12期1284-1291,共8页Chemistry

基　　金：国家级大学生创新训练项目(202010225149);黑龙江省自然科学基金联合引导项目(LH2019C001、LH2020H002);中国博士后科学基金项目(2019M651243);黑龙江博士后基金项目(LBH-Z18013);中央高校基本科研业务费项目(2572018BD06)资助。

摘　　要：G-四链体是一类由Hoogsteen氢键维持稳定的、富含鸟嘌呤的DNA或RNA二级结构。人类基因组中存在大量潜在的形成G-四链体的序列,所形成的G-四链体结构能够调控基因组的稳定性、DNA复制和基因表达,其中包括很多与癌症相关基因。因此寻找能够诱导DNA的G富集区域形成G-四链体结构的配体,进而筛选潜在抗癌药物的先导化合物,已成为癌症治疗研究的热点之一。本文按照靶向的G-四链体结构类型和配体的分子结构进行分类,介绍近年来发现和设计的以G-四链体为靶点的小分子配体在癌症治疗方面的研究进展,分析了相关靶向治疗存在的问题,并对未来的研究方向进行了展望。G-quadruplex is a kind of guanine-rich DNA or RNA secondary structures stabilized by the Hoogsteen hydrogen bonds. A large number of potential G-quadruplex formation motifs are present in the human genome, and the G-quadruplex structures regulate genomic stability, DNA replication, and gene expression, many of which are related to oncogenesis. Therefore, searching for ligands that can induce G-quadruplex formation in the guanine-rich regions of DNA and screening for potential compounds as anticancer drugs represent one of the research hotspots in the field of cancer therapies. This review summarized small molecule ligands that can target G-quadruplex structures. These small molecule ligands are classified based on the types of targeted G-quadruplexes and their molecular structures, the research progress of cancer therapies employing these compounds, the existing issues of their applications are discussed, and future research directions are prospected.

关 键 词：G-四链体 配体 启动子 肿瘤细胞 

分 类 号：R730.5[医药卫生—肿瘤]