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

Ahmed Mostafa Abdelhady, Yu Hirano, Kazumitsu Onizuka, Hidenori Okamura, Yasuo Komatsu, Fumi Nagatsugi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number128257
JournalBioorganic and Medicinal Chemistry Letters
Volume48
DOIs
Publication statusPublished - 2021 Sep 15

Keywords

  • Anti-miRNA
  • Crosslinked duplex
  • Oligonucleotides
  • RISC complex

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Synthesis of crosslinked 2′-OMe RNA duplexes and their application for effective inhibition of miRNA function'. Together they form a unique fingerprint.

Cite this