Synthesis and characterization of 2'-modified-4'-thioRNA: a comprehensive comparison of nuclease stability.
Synthesis and characterization of 2'-modified-4'-thioRNA: a comprehensive comparison of nuclease stability.
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DOI：
10.1093/nar/gkn1088
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发表时间：
2009-03
影响因子：
14.9
通讯作者：
Matsuda A
中科院分区：
文献类型：
--
作者：
Takahashi M;Minakawa N;Matsuda A
本文报道了完全修饰的2′-修饰的4′-硫代RNA（2′-fluoro-4′-thioRNA，F-SRNA）和2′-O-Me-4′-thioRNA（2′-O-Me-4′-thioRNA，Me-SRNA）的合成及其物理和生理特性。在与互补RNA的杂交中，F-SRNA（15聚体）显示出最高的Tm值（相对于天然RNA双链体+16 ° C）。此外，F-SRNA和Me-SRNA在双链体形成中都更喜欢RNA作为互补伴侣，而不是DNA。对单链F-SRNA和Me-SRNA沿着2′-fluoroRNA（FRNA）、2′-O-MeRNA（梅尔纳）、SRNA以及天然RNA和DNA的核酸酶稳定性进行综合比较的结果显示，Me-SRNA具有最高的稳定性，其对S1核酸酶（内切核酸酶）的t1/2值> 24 h，对SVPD（3′-外切核酸酶）的t1/2值为79.2 min。此外，与FRNA（t1/2 = 53.2 min）和MeRNA（t1/2 = 187 min）相比，Me-SRNA在50%人血浆中的稳定性显著提高（t1/2 = 1631 min），FRNA和MeRNA的修饰目前用作治疗性适体的组分。本文的研究结果将有助于开发2′-修饰的4′-thioRNA，特别是Me-SRNA，作为一种新的RNA分子用于治疗应用。
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 (+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 t1/2 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 (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.
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影响因子：
14.9
作者：
Kato, Y;Minakawa, N;Matsuda, A
通讯作者：
Matsuda, A
影响因子：
15
作者：
Inoue, Naonori;Shionoya, Aki;Matsuda, Akira
通讯作者：
Matsuda, Akira
DOI：
10.1089/ard.1995.5.167
发表时间：
1995-09-01
期刊：
ANTISENSE RESEARCH AND DEVELOPMENT
影响因子：
--
作者：
LEYDIER, C;BELLON, L;IMBACH, JL
通讯作者：
IMBACH, JL
影响因子：
14.9
作者：
Matsugami, Akimasa;Ohyama, Takako;Katahira, Masato
通讯作者：
Katahira, Masato
影响因子：
2.9
作者：
Lesnik, EA;Freier, SM
通讯作者：
Freier, SM