Conception and Synthesis of Oxabicyclic Nucleoside Phosphonates as Internucleotidic Phosphate Surrogates in Antisense Oligonucleotide Constructs

Org Lett. 2018 Sep 7;20(17):5296-5299. doi: 10.1021/acs.orglett.8b02233. Epub 2018 Aug 27.

Abstract

The stereocontrolled synthesis of a novel oxabicyclic nucleoside phosphonate comprising a perhydrofuropyran core unit was achieved. It was incorporated in an oligonucleotide sequence as a 5'-3' phosphonate-phosphate insert, and the stability properties of the resulting duplex were measured. The oxabicyclic nucleoside framework was designed so as to restrict rotation around angles γ, δ, and ε of a natural nucleoside.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chemistry Techniques, Synthetic
  • Oligonucleotides, Antisense / chemistry*
  • Oligonucleotides, Antisense / genetics
  • Organophosphonates / chemistry*
  • Phosphates / chemistry*

Substances

  • Oligonucleotides, Antisense
  • Organophosphonates
  • Phosphates