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出 处:《化学通报》2016年第5期387-394,共8页Chemistry
基 金:国家自然科学基金项目(21472197);国家973计划项目(2013CB733701)资助
摘 要:G-四链体是一种由富含鸟嘌呤核酸序列形成的独特的二级结构,广泛分布于真核生物基因组,如端粒DNA、r DNA和一系列基因中的启动子区域。G-四链体结构对很多重要的生理过程如基因的转录、复制、重组以及保持染色体的稳定性方面具有重要作用。G-四链体的特异、高灵敏检测将为进一步了解G-四链体结构在人类细胞基因组中的分布、功能和机制奠定基础,也可能为靶向G-四链体的肿瘤治疗方法提供新的思路。因而过去几十年人们一直致力于开发设计具有高选择性和高灵敏度的G-四链体识别探针,这些探针已经广泛应用于溶液中G-四链体的识别,而且具有良好的选择性。目前也有少数探针能够直接用于检测活体G-四链体结构。本文综述了一些常见的靶向G-四链体的小分子配体,以及它们在染色体和活体细胞G-四链体检测中的应用。笔者希冀本文能为设计识别G-四链体的高性能探针,进一步实现活细胞内G-四链体的检测提供借鉴。G-quadruplexes are non-canonical secondary DNA / RNA structure formed by guanine-rich oligonucleotide sequences,which widely exist in eukaryotic genomes,such as telomeric DNA,r DNA,and promoter regions of oncogenes. G-quadruplex structure may play a pivotal role in the control of a variety of cellar processes including telomere maintenance,replication,transcription,and translation. Detection of the quadruplex structures using the probes with high specificity and sensitivity will help us to explore the distribution,function,and mechanism of G-quadruplexes in human cells,and may also provide new diagnostic and therapeutic approaches of cancer via targeting G-quadruplex. In the last two decades,various targeting G-quadruplex probes which have high selectivity and sensitivity have been designed,and these probes have been used to recognize different G-quadruplex topologies in solutions. A few probes have also been applied to recognize G-quadruplex in vivo. This article reviews the typical probes targeting G-quadruplexes as well as their application in detection G-quadruplexes in chromosome and cell level. Authors hope this paper can provide a certain reference for design of G-quadruplex-targeting probes and further realization of G-quadruplex detection in living cells.
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