Small molecule targeting of biologically relevant RNA tertiary and quaternary structures.
Small molecule targeting of biologically relevant RNA tertiary and quaternary structures.
复制标题
生物相关核糖核酸三级和四级结构的小分子靶向。
DOI：
10.1016/j.chembiol.2021.03.003
复制
发表时间：
2021-05-20
影响因子：
8.6
通讯作者：
Hargrove AE
中科院分区：
文献类型：
--
作者：
Zafferani M;Hargrove AE
在为非编码RNA开发小分子配体方面的初步成功突显了它们作为治疗靶点的潜力。最近，这些成功得益于生物物理和结构技术的进步，用于识别和表征更复杂的RNA结构；这些更高水平的折叠提供了蛋白质样的结合口袋，为设计小分子提供了机会，这些小分子可以实现往往很难在一级和二级结构水平上获得的一定程度的选择性。更具体地说，识别RNA的三级和四级结构，并用小分子配体靶向这些结构，使研究人员能够探索几种人类疾病，并产生了有希望的临床候选药物。在这篇综述中，我们重点介绍了一系列不同的和令人兴奋的成功以及导致它们发现的实验方法。这些研究包括以RNA为中心的分析和配体的最新发展，这些分析和配体提供了对RNA靶标化学探针的亲和力和生物学结果负责的特征的洞察。这份报告强调了选择性地以RNA三级和四级结构为目标的潜在和正在出现的机会，作为更好地了解并最终治疗许多疾病的途径。Zafferani等人。回顾导致小分子靶向RNA三级和四级结构成功的各种方法。这篇综述强调了开发化学探针的机会和挑战，这些探针针对的是生命所有领域中数量呈指数级增长的功能表征的RNA三级和四级结构。
Initial successes in developing small molecule ligands for non-coding RNAs have underscored their potential as therapeutic targets. More recently, these successes have been aided by advances in biophysical and structural techniques for identification and characterization of more complex RNA structures; these higher-level folds present protein-like binding pockets that offer opportunities to design small molecules that could achieve a degree of selectivity often hard to obtain at the primary and secondary structure level. More specifically, identification of RNA tertiary and quaternary structures and targeting these structures with small molecule ligands have allowed researchers to probe several human diseases and have resulted in promising clinical candidates. In this review we highlight a selection of diverse and exciting successes and the experimental approaches that led to their discovery. These studies include examples of recent developments in RNA-centric assays and ligands that provide insight into the features responsible for the affinity and biological outcome of RNA-targeted chemical probes. This report highlights the potential and emerging opportunities to selectively target RNA tertiary and quaternary structures as a route to better understand and, ultimately, treat many diseases. Zafferani et al. review diverse approaches that resulted in the successful small molecule targeting of RNA tertiary and quaternary structures. This review highlights the opportunities and challenges in developing chemical probes that target the exponentially growing number of functionally characterized RNA tertiary and quaternary structures across all domains of life.
登录
查看更多内容
影响因子：
4
作者：
Furukawa, Kazuhiro;Gu, Hongzhou;Sudarsan, Narasimhan;Hayakawa, Yoshihiro;Hyodo, Mamoru;Breaker, Ronald R.
通讯作者：
Breaker, Ronald R.
影响因子：
14.9
作者：
Bugaut A;Balasubramanian S
通讯作者：
Balasubramanian S
影响因子：
8.4
作者：
Cressina, Elena;Chen, Liuhong;Smith, Alison G.
通讯作者：
Smith, Alison G.
影响因子：
16.6
作者：
Donlic, Anita;Morgan, Brittany S.;Hargrove, Amanda E.
通讯作者：
Hargrove, Amanda E.
影响因子：
7.3
作者：
Costales, Matthew G.;Childs-Disney, Jessica L.;Disney, Matthew D.
通讯作者：
Disney, Matthew D.