Synthesis and biophysical evaluation of 3′-Me-α-L-LNA - Substitution in the minor groove of α-L-LNA duplexes
Synthesis and biophysical evaluation of 3′-Me-α-L-LNA - Substitution in the minor groove of α-L-LNA duplexes
复制标题
DOI：
10.1016/j.bmcl.2011.06.104
复制
发表时间：
2011-08-15
影响因子：
2.7
通讯作者：
Swayze, Eric E.
中科院分区：
文献类型：
--
作者：
Seth, Punit P.;Allerson, Charles A.;Swayze, Eric E.
本文报道了3 '-Me-alpha-L-LNA的合成和生物物理学评价。核苷结构单元亚磷酰胺的合成从二丙酮葡萄糖开始完成。通过氢化物介导的环外环氧化物的打开以所需构型引入3 '-Me基团。通过氧化/还原顺序实现2 '-羟基的转化，然后环化到5'-离去基团上以组装[2.2.1]环系统。3 '-Me-alpha-L-LNA修饰的寡核苷酸的生物物理评价显示出与alpha-L-LNA相似的良好的双链体热稳定性质。错配辨别实验显示，与相关核酸类似物相比，3 ′-Me-alpha-L-LNA具有对GU摆动碱基对的略微增强的辨别特性。(C)2011爱思唯尔有限公司保留所有权利。
The synthesis and biophysical evaluation of 3'-Me-alpha-L-LNA is reported. The synthesis of the nucleoside building block phosphoramidite was accomplished starting from diacetone glucose. The 3'-Me group was introduced in the desired configuration by hydride mediated opening of an exocyclic epoxide. Inversion of the 2'-hydroxyl group was achieved by means of an oxidation/reduction sequence followed by cyclization onto a 5'-leaving group to assemble the [2.2.1] ring system. Biophysical evaluation of 3'-Me-alpha-L-LNA modified oligonucleotides showed good duplex thermal stabilizing properties which were similar to alpha-L-LNA. Mismatch discrimination experiments revealed that 3'-Me-alpha-L-LNA possess slightly enhanced discrimination properties for the GU wobble base-pair as compared to related nucleic acid analogs. (C) 2011 Elsevier Ltd. All rights reserved.