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寡核苷酸类似物作为非编码 RNA(ncRNA)表达和功能的调节剂:新兴的治疗应用。

Oligonucleotide analogues as modulators of the expression and function of noncoding RNAs (ncRNAs): emerging therapeutics applications.

机构信息

Università di Napoli "Federico II" , Dipartimento di Farmacia, via Mezzocannone 16, 80134 Napoli, Italy.

出版信息

J Med Chem. 2014 Dec 26;57(24):10220-40. doi: 10.1021/jm5006594. Epub 2014 Oct 21.

Abstract

ncRNAs are emerging as key regulators of physiological and pathological processes and therefore have been identified as pharmacological targets and as markers for some diseases. Oligonucleotide analogues represent so far the most widely employed tool for the modulation of the expression of ncRNAs. In this perspective we briefly describe most of the known classes of ncRNAs and then we discuss the design and the applications of oligonucleotide analogues for their targeting. The effects of modifications of the chemical structure of the oligonucleotides on properties such as the binding affinity toward targets and off targets, and the stability to degradation and their biological effects (when known) are discussed. Examples of molecules currently used in clinical trials are also reported.

摘要

非编码 RNA 作为生理和病理过程的关键调节剂而出现,因此被鉴定为一些疾病的药物靶点和标志物。寡核苷酸类似物是迄今为止用于调节非编码 RNA 表达的最广泛使用的工具。在这方面,我们简要描述了已知的大多数非编码 RNA 类别,然后讨论了针对它们的寡核苷酸类似物的设计和应用。讨论了寡核苷酸化学结构修饰对与靶标和非靶标结合亲和力、对降解的稳定性以及生物学效应(如果已知)等性质的影响。还报告了目前正在临床试验中使用的分子的例子。

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