Synthesis of crosslinked 2′-OMe RNA duplexes and their application for effective inhibition of miRNA function
Synthesis of crosslinked 2′-OMe RNA duplexes and their application for effective inhibition of miRNA function
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DOI：
10.1016/j.bmcl.2021.128257
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发表时间：
2021-07-12
影响因子：
2.7
通讯作者：
Nagatsugi, Fumi
中科院分区：
文献类型：
--
作者：
Abdelhady, Ahmed Mostafa;Hirano, Yu;Nagatsugi, Fumi
核酸链间交联是寡核苷酸与RNA通过共价键形成稳定复合物的策略之一。我们先前报道了具有2-氨基-6-乙烯基嘌呤（AVP）的完全2 '-O-甲基化（2'-OMe）RNA表现出与靶RNA中的尿嘧啶的有效交联。在本研究中，我们建立了一种化学方法来有效地合成交联的2 '-OMe RNA双链体，并制备了在末端序列处含有反义靶向miR-21和交联双链体的抗miRNA寡核苷酸（AMOs）。这些AMO显示出比具有锁核酸（LNA）残基的市售miR-21抑制剂显著更高的抗miRNA活性。
The interstrand crosslinking of nucleic acids is one of the strategies to create the stable complex between an oligonucleotide and RNA by covalent bond formation. We previously reported that fully 2'-O-methylated (2'-OMe) RNAs having the 2-amino-6-vinylpurine (AVP) exhibited an efficient crosslinking to uracil in the target RNA. In this study, we established a chemical method to efficiently synthesize the crosslinked 2'-OMe RNA duplexes using AVP and prepared the anti-miRNA oligonucleotides (AMOs) containing the antisense targeting miR-21 and crosslinked duplex at the terminal sequences. These AMOs showed a markedly higher anti miRNA activity than that of the commercially-available miR-21 inhibitor which has locked nucleic acid (LNA) residues.