Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells.
Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells.
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DOI：
10.1146/annurev-pharmtox-010715-103910
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发表时间：
2016
影响因子：
12.5
通讯作者：
Disney MD
中科院分区：
文献类型：
--
作者：
Childs-Disney JL;Disney MD
RNA已成为治疗干预和化学探针的一个越来越重要的目标，这些化学探针可以解剖和操纵其细胞功能。新出现的靶点包括已被证明直接导致癌症、代谢紊乱和遗传疾病的人类RNA。在这篇综述中，我们描述了获得靶向RNA的生物活性化合物的各种途径，特别强调小分子的发展。我们使用这些案例来描述正在开发的靶向验证方法，包括靶向切割，经典的下拉实验和共价交联。因此，工具可用于设计靶向RNA的小分子并鉴定作为其靶的细胞RNA。
RNA has become an increasingly important target for therapeutic interventions and for chemical probes that dissect and manipulate its cellular function. Emerging targets include human RNAs that have been shown to directly cause cancer, metabolic disorders, and genetic disease. In this review, we describe various routes to obtain bioactive compounds that target RNA, with a particular emphasis on the development of small molecules. We use these cases to describe approaches that are being developed for target validation, which include target-directed cleavage, classic pull-down experiments, and covalent cross-linking. Thus, tools are available to design small molecules to target RNA and to identify the cellular RNAs that are their targets.