Characterization of fully 2′-modified oligoribonucleotide hetero- and homoduplex hybridization and nuclease sensitivity (original) (raw)
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ISIS Pharmaceuticals
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ISIS Pharmaceuticals
2292 Faraday Avenue, Carlsbad, CA 92008, USA
Search for other works by this author on:
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ISIS Pharmaceuticals
2292 Faraday Avenue, Carlsbad, CA 92008, USA
Search for other works by this author on:
,
ISIS Pharmaceuticals
2292 Faraday Avenue, Carlsbad, CA 92008, USA
Search for other works by this author on:
,
ISIS Pharmaceuticals
2292 Faraday Avenue, Carlsbad, CA 92008, USA
Search for other works by this author on:
,
ISIS Pharmaceuticals
2292 Faraday Avenue, Carlsbad, CA 92008, USA
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ISIS Pharmaceuticals
2292 Faraday Avenue, Carlsbad, CA 92008, USA
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Received:
13 January 1995
Revision received:
29 March 1995
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Lendell L. Cummins, Stephen R. Owens, Lisa M. Risen, Elena A. Lesnik, Susan M. Freier, Danny McGee, Charles J. Guinosso, P. Dan Cook, Characterization of fully 2′-modified oligoribonucleotide hetero- and homoduplex hybridization and nuclease sensitivity, Nucleic Acids Research, Volume 23, Issue 11, 11 June 1995, Pages 2019–2024, https://doi.org/10.1093/nar/23.11.2019
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Abstract
The nuclease stability and melting temperatures ( _T_m ) were compared for fully modified oligoribonucleotide sequences containing 2′-fluoro, 2′- O -methyl, 2′- O -propyl and 2′- O -pentyl nucleotides. Duplexes formed between 2′ modified oligoribonucleotides and RNA have typical A-form geometry as observed by circular dichroism spectroscopy. Modifications, with the exception of 2′- O -pentyl, were observed to increase the _T_m of duplexes formed with complementary RNA. Modified homoduplexes showed significantly higher _T_m s, with the following _T_m order: 2′-fluoro:2′fluoro > 2′- O -propyl:2′- O -propyl > 2′- O -methyl:2′- O -methyl > RNA:RNA > DNA:DNA. The nuclease stability of 2′-modified oligoribonucleotides was examined using snake venom phosphodiesterase (SVPD) and nuclease S1. The stability imparted by 2′ modifications was observed to correlate with the size of the modification. An additional level of nuclease stability was present in oligoribonucleotides having the potential for forming secondary structure, but only for 2′ modified oligoribonucleotides and not for 2′-deoxy oligoribonucleotides.
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