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Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability
We report herein the synthesis and physical and physiological characterization of fully modified 2′-modified-4′-thioRNAs, i.e. 2′-fluoro-4′-thioRNA (F-SRNA) and 2′-O-Me-4′-thioRNA (Me-SRNA), which can be considered as a hybrid chemical modification based on 2′-modified oligonucleotides (ONs) and 4′-...
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651785/ https://www.ncbi.nlm.nih.gov/pubmed/19151085 http://dx.doi.org/10.1093/nar/gkn1088 |
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author | Takahashi, Mayumi Minakawa, Noriaki Matsuda, Akira |
author_facet | Takahashi, Mayumi Minakawa, Noriaki Matsuda, Akira |
author_sort | Takahashi, Mayumi |
collection | PubMed |
description | We report herein the synthesis and physical and physiological characterization of fully modified 2′-modified-4′-thioRNAs, i.e. 2′-fluoro-4′-thioRNA (F-SRNA) and 2′-O-Me-4′-thioRNA (Me-SRNA), which can be considered as a hybrid chemical modification based on 2′-modified oligonucleotides (ONs) and 4′-thioRNA (SRNA). In its hybridization with a complementary RNA, F-SRNA (15mer) showed the highest T(m) value (+16°C relative to the natural RNA duplex). In addition, both F-SRNA and Me-SRNA preferred RNA as a complementary partner rather than DNA in duplex formation. The results of a comprehensive comparison of nuclease stability of single-stranded F-SRNA and Me-SRNA along with 2′-fluoroRNA (FRNA), 2′-O-MeRNA (MeRNA), SRNA, and natural RNA and DNA, revealed that Me-SRNA had the highest stability with t(1/2) values of > 24 h against S1 nuclease (an endonuclease) and 79.2 min against SVPD (a 3′-exonuclease). Moreover, the stability of Me-SRNA was significantly improved in 50% human plasma (t(1/2) = 1631 min) compared with FRNA (t(1/2) = 53.2 min) and MeRNA (t(1/2) = 187 min), whose modifications are currently used as components of therapeutic aptamers. The results presented in this article will, it is hoped, contribute to the development of 2′-modified-4′-thioRNAs, especially Me-SRNA, as a new RNA molecule for therapeutic applications. |
format | Text |
id | pubmed-2651785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26517852009-03-13 Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability Takahashi, Mayumi Minakawa, Noriaki Matsuda, Akira Nucleic Acids Res Chemistry and Synthetic Biology We report herein the synthesis and physical and physiological characterization of fully modified 2′-modified-4′-thioRNAs, i.e. 2′-fluoro-4′-thioRNA (F-SRNA) and 2′-O-Me-4′-thioRNA (Me-SRNA), which can be considered as a hybrid chemical modification based on 2′-modified oligonucleotides (ONs) and 4′-thioRNA (SRNA). In its hybridization with a complementary RNA, F-SRNA (15mer) showed the highest T(m) value (+16°C relative to the natural RNA duplex). In addition, both F-SRNA and Me-SRNA preferred RNA as a complementary partner rather than DNA in duplex formation. The results of a comprehensive comparison of nuclease stability of single-stranded F-SRNA and Me-SRNA along with 2′-fluoroRNA (FRNA), 2′-O-MeRNA (MeRNA), SRNA, and natural RNA and DNA, revealed that Me-SRNA had the highest stability with t(1/2) values of > 24 h against S1 nuclease (an endonuclease) and 79.2 min against SVPD (a 3′-exonuclease). Moreover, the stability of Me-SRNA was significantly improved in 50% human plasma (t(1/2) = 1631 min) compared with FRNA (t(1/2) = 53.2 min) and MeRNA (t(1/2) = 187 min), whose modifications are currently used as components of therapeutic aptamers. The results presented in this article will, it is hoped, contribute to the development of 2′-modified-4′-thioRNAs, especially Me-SRNA, as a new RNA molecule for therapeutic applications. Oxford University Press 2009-03 2009-01-16 /pmc/articles/PMC2651785/ /pubmed/19151085 http://dx.doi.org/10.1093/nar/gkn1088 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Chemistry and Synthetic Biology Takahashi, Mayumi Minakawa, Noriaki Matsuda, Akira Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability |
title | Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability |
title_full | Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability |
title_fullStr | Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability |
title_full_unstemmed | Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability |
title_short | Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability |
title_sort | synthesis and characterization of 2′-modified-4′-thiorna: a comprehensive comparison of nuclease stability |
topic | Chemistry and Synthetic Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651785/ https://www.ncbi.nlm.nih.gov/pubmed/19151085 http://dx.doi.org/10.1093/nar/gkn1088 |
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