PMID: 8604321Feb 15, 1996Paper

Antisense oligonucleotide containing an internal, non-nucleotide-based linker promote site-specific cleavage of RNA

Nucleic Acids Research
M A ReynoldsL J Arnold

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.

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Citations

Mar 9, 2012·Applied Microbiology and Biotechnology·Richa GuptaPrince Sharma
Apr 18, 2006·Journal of Biomolecular Structure & Dynamics·Nadezhda L MironovaValentin V Vlassov
Apr 15, 2011·Nucleosides, Nucleotides & Nucleic Acids·Anthony D Saleh, Paul S Miller
Aug 1, 1997·Antisense & Nucleic Acid Drug Development·R Häner, J Hall
Mar 29, 2007·Nucleic Acids Research·N L MironovaM A Zenkova
Jul 8, 2008·Chembiochem : a European Journal of Chemical Biology·Jesus RazkinLars Baltzer
Dec 17, 2005·Organic & Biomolecular Chemistry·Teija Niittymäki, Harri Lönnberg
Dec 4, 2004·Organic Letters·Sylvie PicardPhilippe Uriac
Apr 17, 2001·Nucleosides, Nucleotides & Nucleic Acids·K ShinozukaH Sawai
Jun 5, 2016·Applied and Environmental Microbiology·Loïc DecreyTamar Kohn
Mar 4, 2003·Chemical Communications : Chem Comm·Andrew WhitneyShankar Balasubramanian
Apr 4, 1997·The Journal of Organic Chemistry·Makoto Komiyama, Koichi Yoshinari
Mar 29, 2000·Journal of Pharmaceutical Sciences·D Pogocki, C Schöneich
Sep 20, 2000·Bioconjugate Chemistry·C H Tung, S Stein
Aug 22, 2002·Journal of the American Chemical Society·Leonard LermerDavid M Perrin

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