Chemical synthesis of LNA-2-thiouridine and its influence on stability and selectivity of oligonucleotide binding to RNA.
Chemical synthesis of LNA-2-thiouridine and its influence on stability and selectivity of oligonucleotide binding to RNA.
复制标题
DOI：
10.1021/bi901506f
复制
发表时间：
2009-11-24
期刊：
影响因子：
2.9
通讯作者：
Kierzek, Ryszard
中科院分区：
文献类型：
--
作者：
Carlucci, Marta;Kierzek, Elzbieta;Olejnik, Anna;Turner, Douglas H.;Kierzek, Ryszard
与RNA的杂交对于许多应用是重要的，包括反义治疗、RNA干扰和微阵列筛选。A-U和G-U碱基对的相似热力学稳定性导致难以选择性结合匹配和错配的RNA双链体。此外，A-U对比G-C对弱，因此当存在许多A-U对时，结合有时较弱。然而，已知用2-硫代尿苷替代尿苷显著改善结合和选择性。为了测试结合的额外改进和结合A超过G的特异性，首次合成LNA-2-硫尿苷并掺入许多LNA-2-O-甲基RNA/RNA双链体中。使用UV熔融来测量用2 ′-O-甲基-2-硫代尿苷或LNA-2-硫代尿苷替代2 ′-O-甲基尿苷的热力学效应。2-硫代尿苷通常增强结合和选择性。当单个2-硫代尿苷位于双链体的内部位置时，选择性得到优化。
Hybridization to RNA is important for many applications, including antisense therapeutics, RNA interference, and microarray screening. Similar thermodynamic stabilities of A-U and G-U base pairs result in difficulties in selective binding of matched and mismatched RNA duplexes. Moreover, A-U pairs are weaker than G-C pairs so that binding is sometimes weak when many A-U pairs are present. It is known, however, that replacement of uridine with 2-thiouridine significantly improves binding and selectivity. To test for additional improvement of binding and of the specificity for binding A over G, LNA-2-thiouridine was synthesized for the first time and incorporated into many LNA-2-O-methylRNA/RNA duplexes. UV melting was used to measure the thermodynamic effect of replacing 2'-O-methyluridine with 2'-O-methyl-2-thiouridine or LNA-2-thiouridine. The 2-thiouridine usually enhances binding and selectivity. Selectivity is optimized when a single 2-thiouridine is placed at an internal position in a duplex.
登录
查看更多内容
影响因子：
2.1
作者：
Koshkin, AA;Singh, SK;Wengel, J
通讯作者：
Wengel, J
影响因子：
2.9
作者：
Kaur, Harleen;Wengel, Jesper;Maiti, Souvik
通讯作者：
Maiti, Souvik
影响因子：
3.2
作者：
Fluiter, K;Frieden, M;Baas, F
通讯作者：
Baas, F
影响因子：
14.9
作者：
Elmén J;Thonberg H;Ljungberg K;Frieden M;Westergaard M;Xu Y;Wahren B;Liang Z;Ørum H;Koch T;Wahlestedt C
通讯作者：
Wahlestedt C
影响因子：
15
作者：
AGRIS, PF;SIERZPUTOWSKAGRACZ, H;NAWROT, B
通讯作者：
NAWROT, B