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Synthesis and characterization of 2'-modified-4'-thioRNA: a comprehensive comparison of nuclease stability

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Title: Synthesis and characterization of 2'-modified-4'-thioRNA: a comprehensive comparison of nuclease stability
Authors: Takahashi, Mayumi Browse this author
Minakawa, Noriaki Browse this author
Matsuda, Akira Browse this author
Issue Date: Jan-2009
Publisher: Oxford University Press
Journal Title: Nucleic Acids Research
Volume: 37
Issue: 4
Start Page: 1353
End Page: 1362
Publisher DOI: 10.1093/nar/gkn1088
Abstract: 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 Tm value (+168C 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 t1/2 values of>24 h against S1 nuclease (an endonuclease) and 79.2 min against SVPD (a ’-exonuclease). Moreover, the stability of Me-SRNA was significantly improved in 50% human plasma (t1/2 = 1631 min) compared with FRNA (t1/2 = 53.2 min) and MeRNA (t1/2 = 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.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 彰

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