Hydrolysis of bulged nucleotides in hybrids formed by rna and imidazole-derivatized oligo-2′-O-methylribonucleotides

Anthony D. Saleh, Paul S. Miller

Research output: Contribution to journalArticle

Abstract

In order to enhance the efficacy of small antisense molecules, we examined a series of antisense oligonucleotides derivatized with functional groups designed to enable them to hydrolyze their RNA target. Solid phase synthetic methods were used to prepare imidazole-derivatized antisense oligo-2′-O-methylribonucleotides. Upon binding, these oligonucleotides create internal bulged bases in the target RNA that serve as sites for hydrolysis. We observed that an oligonucleotide derivatized with a side chain containing two imidazole groups was capable of hydrolyzing 58% of its RNA target when incubated with the target for 48 hours at 37°C and physiological pH.

Original languageEnglish (US)
Pages (from-to)235-255
Number of pages21
JournalNucleosides, Nucleotides and Nucleic Acids
Volume30
Issue number3
DOIs
StatePublished - May 23 2011

Keywords

  • RNA
  • antisense
  • bioconjugate
  • hydrolysis
  • oligonucleotide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

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