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超越核糖与磷酸：用于结构功能研究及治疗应用的特定核酸修饰

Beyond ribose and phosphate: Selected nucleic acid modifications for structure-function investigations and therapeutic applications.

作者信息

Liczner Christopher, Duke Kieran, Juneau Gabrielle, Egli Martin, Wilds Christopher J

机构信息

Department of Chemistry and Biochemistry, Concordia University, Montréal, Québec H4B 1R6, Canada.

Department of Biochemistry, Vanderbilt Institute of Chemical Biology, and Center for Structural Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, United States.

出版信息

Beilstein J Org Chem. 2021 Apr 28;17:908-931. doi: 10.3762/bjoc.17.76. eCollection 2021.

DOI:10.3762/bjoc.17.76
PMID:33981365
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8093555/
Abstract

Over the past 25 years, the acceleration of achievements in the development of oligonucleotide-based therapeutics has resulted in numerous new drugs making it to the market for the treatment of various diseases. Oligonucleotides with alterations to their scaffold, prepared with modified nucleosides and solid-phase synthesis, have yielded molecules with interesting biophysical properties that bind to their targets and are tolerated by the cellular machinery to elicit a therapeutic outcome. Structural techniques, such as crystallography, have provided insights to rationalize numerous properties including binding affinity, nuclease stability, and trends observed in the gene silencing. In this review, we discuss the chemistry, biophysical, and structural properties of a number of chemically modified oligonucleotides that have been explored for gene silencing.

摘要

在过去25年里，基于寡核苷酸的治疗药物开发成果加速涌现，众多新药已上市用于治疗各种疾病。通过修饰核苷和固相合成制备的具有支架结构改变的寡核苷酸，产生了具有有趣生物物理特性的分子，这些分子能够与靶点结合，并被细胞机制所耐受从而产生治疗效果。诸如晶体学等结构技术，为解释包括结合亲和力、核酸酶稳定性以及基因沉默中观察到的趋势等众多特性提供了见解。在本综述中，我们讨论了一些已被探索用于基因沉默的化学修饰寡核苷酸的化学、生物物理和结构特性。

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