Antisense Oligonucleotides Containing an Internal, Non-Nucleotide-Based Linker Promote Site-Specific Cleavage of RNA
- 1 February 1996
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 24 (4) , 760-765
- https://doi.org/10.1093/nar/24.4.760
Abstract
We have designed and synthesized a series of novel antisense methylphosphonate oligonucleotide (MPO) cleaving agents that promote site-specific cleavage on a complementary RNA target. These MPOs contain a non- nucleotide-based linking moiety near the middle of the sequence in place of one of the nucleotide bases. The region surrounding the unpaired base on the RNA strand (i.e. the one directly opposite the non-nucleotide-linker) is sensitive to hydrolytic cleavage catalyzed by ethylenediamine hydrochloride. Furthermore, the regions of the RNA comprising hydrogen bonded domains are resistant to cleavage compared with single-stranded RNA alone. Several catalytic moieties capable of supporting acid/base hydrolysis were coupled to the non-nucleotide-based linker via simple aqueous coupling chemistries. When tethered to the MPO in this manner these moieties are shown to catalyze site-specific cleavage on the RNA target without any additional catalyst.Keywords
This publication has 38 references indexed in Scilit:
- A non-nucleotide-based linking method for the preparation of psoralen-derivatized methylphosphonate oligonucleotidesBioconjugate Chemistry, 1992
- Endocyclic and exocyclic cleavage of phosphorane monoanion: a detailed mechanism of the RNase A transphosphorylation stepJournal of the American Chemical Society, 1992
- Manipulating the stoichiometry and strength of phosphodiester binding to a bisguanidine cleft in DMSO/water solutionsThe Journal of Organic Chemistry, 1992
- Catalytic transesterification and hydrolysis of RNA by zinc(II) complexesInorganic Chemistry, 1991
- Oligoamines as simple and efficient catalysts for RNA hydrolysisJournal of the American Chemical Society, 1991
- Toward Chemical Ribonucleases. 2. Synthesis and Characterization of Nucleoside-Bipyridine Conjugates. Hydrolytic Cleavage of RNA by Their Copper(II) ComplexesJournal of the American Chemical Society, 1991
- Simulation analysis of structures on the reaction pathway of RNAse AJournal of the American Chemical Society, 1990
- Geometric evidence on the ribonuclease model mechanismJournal of the American Chemical Society, 1989
- Basic polypeptides accelerate the hydrolysis of ribonucleic acidsJournal of the American Chemical Society, 1988
- Sequence-specific scission of RNA by 1,10-phenanthroline-copper linked to deoxyoligonucleotidesJournal of the American Chemical Society, 1988