Childs-Disney Jessica L, Disney Matthew D
Department of Chemistry, The Scripps Research Institute, Jupiter, Florida 33458; email:
Annu Rev Pharmacol Toxicol. 2016;56:123-40. doi: 10.1146/annurev-pharmtox-010715-103910. Epub 2015 Oct 22.
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.
RNA已成为治疗干预以及用于剖析和操纵其细胞功能的化学探针的一个日益重要的靶点。新出现的靶点包括已被证明可直接导致癌症、代谢紊乱和遗传疾病的人类RNA。在本综述中，我们描述了获得靶向RNA的生物活性化合物的各种途径，特别强调了小分子的开发。我们用这些案例来描述正在开发的用于靶点验证的方法，包括靶向切割、经典的下拉实验和共价交联。因此，现在有工具可用于设计靶向RNA的小分子，并识别其作为靶点的细胞RNA。
