Synthesis of 2'-O-(N-methylcarbamoylethyl) 5-methyl-2-thiouridine and its application to splice-switching oligonucleotides

Bioorg Med Chem Lett. 2019 Jan 15;29(2):160-163. doi: 10.1016/j.bmcl.2018.12.005. Epub 2018 Dec 4.

Abstract

The effect of 2'-O-(N-methylcarbamoyl)ethyl (MCE) modification on splice-switching oligonucleotides (SSO) was systematically evaluated. The incorporation of five MCE nucleotides at the 5'-termini of SSOs effectively improved the splice switching effect. In addition, the incorporation of 2'-O-(N-methylcarbamoylethyl)-5-methyl-2-thiouridine (s2TMCE), a duplex-stabilizing nucleotide with an MCE modification, into SSOs further improved splice switching. These SSOs may be useful for the treatment of genetic diseases associated with splicing errors.

Keywords: 2′-O-modification; Chemically modified RNA; Exon skipping; Nucleic acid therapeutics; Splice-switching oligonucleotide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Structure
  • Oligonucleotides / chemistry*
  • Thiouridine / agonists
  • Thiouridine / chemical synthesis
  • Thiouridine / chemistry*

Substances

  • Oligonucleotides
  • Thiouridine