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 language | English (US) |
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Pages (from-to) | 235-255 |
Number of pages | 21 |
Journal | Nucleosides, Nucleotides and Nucleic Acids |
Volume | 30 |
Issue number | 3 |
DOIs | |
State | Published - 2011 |
Externally published | Yes |
Keywords
- RNA
- antisense
- bioconjugate
- hydrolysis
- oligonucleotide
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Genetics