2024-03-28T20:21:11Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/469502023-11-21T07:22:30Zhdl_2115_20044hdl_2115_124Synthesis and characterization of 2'-modified-4'-thioRNA: a comprehensive comparison of nuclease stabilityTakahashi, MayumiMinakawa, NoriakiMatsuda, Akiraopen access460We 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.Oxford University Press2009-01engjournal articleVoRhttp://hdl.handle.net/2115/46950https://doi.org/10.1093/nar/gkn10880305-10481362-4962Nucleic Acids Research37413531362https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/46950/1/404_09%20NAR%20Takahashi.pdfapplication/pdf1.11 MB2009-01