Synthesis and duplex-forming ability of oligonucleotides modified with 4'-C,5'-C-methylene-bridged nucleic acid (4',5'-BNA)

Bioorg Med Chem. 2021 Sep 15:46:116359. doi: 10.1016/j.bmc.2021.116359. Epub 2021 Aug 8.

Abstract

We describe herein the design and synthesis of 4'-C,5'-C-methylene-bridged nucleic acid (4',5'-BNA), a novel artificial nucleic acid with the torsion angle γ in a non-canonical +ac range. The 4',5'-BNA phosphoramidite bearing a thymine nucleobase was synthesized from a commercially available thymidine analog in 11 steps and successfully incorporated into oligonucleotides. The resulting oligonucleotides were evaluated for their duplex-forming ability toward single-stranded DNA and RNA.

Keywords: Artificial nucleic acid; Duplex-forming ability; Nuclease resistance; Therapeutic oligonucleotide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / chemistry
  • DNA / chemical synthesis*
  • DNA / chemistry
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry*
  • RNA / chemical synthesis*
  • RNA / chemistry

Substances

  • Bridged-Ring Compounds
  • Oligonucleotides
  • RNA
  • DNA