Synthesis and biophysical properties of 5'-thio-2',4'-BNA/LNA oligonucleotide

Bioorg Med Chem. 2018 Jul 23;26(12):3634-3638. doi: 10.1016/j.bmc.2018.05.040. Epub 2018 May 23.

Abstract

Phosphorothioate modification of oligonucleotides is one of the most promising chemical modifications in nucleic acid therapeutics. Structurally similar 5'-thio or phosphorothiolate-modified nucleotides, in which the 5'-bridging oxygen atom is replaced with a sulfur atom, are attracting attention and gaining importance in oligonucleotide-based research. In our present study, we synthesized 5'-thio-2',4'-BNA/LNA monomers bearing thymine or 5-methylcytosine nucleobase. The 5'-thio-2',4'-BNA/LNA monomers were successfully incorporated into target oligonucleotides, and their nuclease stability and binding affinity with complementary strands were evaluated.

Keywords: 2′,4′-BNA; Binding affinity; LNA; Nuclease stability; Phosphorothiolate; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged-Ring Compounds / chemistry
  • Exonucleases / metabolism
  • Nucleic Acid Conformation
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry*
  • Oligonucleotides / metabolism
  • Sulfhydryl Compounds / chemistry*
  • Transition Temperature

Substances

  • Bridged-Ring Compounds
  • Oligonucleotides
  • Sulfhydryl Compounds
  • locked nucleic acid
  • Exonucleases