Synthesis of crosslinked 2′-OMe RNA duplexes and their application for effective inhibition of miRNA function

被引：7

作者：

Abdelhady, Ahmed Mostafa ^{[1
,2
,3
]}

Hirano, Yu ^{[4
]}

Onizuka, Kazumitsu ^{[1
,2
,5
]}

Okamura, Hidenori ^{[1
,2
]}

Komatsu, Yasuo ^{[4
]}

Nagatsugi, Fumi ^{[1
,2
]}

机构：

[1] Tohoku Univ, Inst Multidisciplinary Res Adv Mat, Aoba Ku, 2-1-1 Katahira, Sendai, Miyagi 9808577, Japan

[2] Tohoku Univ, Grad Sch Sci, Dept Chem, Aoba Ku, Sendai, Miyagi 9808578, Japan

[3] Al Azhar Univ, Fac Sci, Dept Chem, Cairo 11884, Egypt

[4] Natl Inst Adv Ind Sci & Technol, Bioprod Res Inst, Toyohira Ku, 2-17-2-1 Tsukisamu Higashi, Sapporo, Hokkaido 0628517, Japan

[5] Tohoku Univ, Div Estab Frontier Sci Org Adv Studies, Aoba Ku, Sendai, Miyagi 9808577, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2021年 / 48卷

基金：

日本学术振兴会;

关键词：

Anti-miRNA; Crosslinked duplex; Oligonucleotides; RISC complex; NUCLEIC-ACID; TARGETING MICRORNAS; LINKING; DNA; OLIGONUCLEOTIDE; 2-AMINO-6-VINYLPURINE; APOPTOSIS; PROBES; ANALOG;

D O I：

10.1016/j.bmcl.2021.128257

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页数：5

共 40 条

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