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首页> 外文期刊>Acta crystallographica.Section D Biological crystallography. >A regular thymine tetrad and a peculiar supramolecular assembly in the first crystal structure of an all-LNA G-quadruplex
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A regular thymine tetrad and a peculiar supramolecular assembly in the first crystal structure of an all-LNA G-quadruplex

机译：常规的胸腺嘧啶四分体和独特的超分子组装的晶体结构的all-LNA G-quadruplex

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摘要

Locked nucleic acids (LNAs) are formed by bicyclic ribonucleotides where the O2′ and C4′ atoms are linked through a methylene bridge and the sugar is blocked in a 3′-endo conformation. They represent a promising tool for therapeutic and diagnostic applications and are characterized by higher thermal stability and nuclease resistance with respect to their natural counterparts. However, structural descriptions of LNA-containing quadruplexes are rather limited, since few NMR models have been reported in the literature. Here, the first crystallographically derived model of an all-LNA-substituted quadruplex-forming sequence 5′-TGGGT-3′ is presented refined at 1.7 ? resolution. This high-resolution crystallographic analysis reveals a regular parallel G-quadruplex arrangement terminating in a well defined thymine tetrad at the 3′-end. The detailed picture of the hydration pattern reveals LNA-specific features in the solvent distribution. Interestingly, two closely packed quadruplexes are present in the asymmetric unit. They face one another with their 3′-ends giving rise to a compact higher-order structure. This new assembly suggests a possible way in which sequential quadruplexes can be disposed in the crowded cell environment. Furthermore, as the formation of ordered structures by molecular self-assembly is an effective strategy to obtain nanostructures, this study could open the way to the design of a new class of LNA-based building blocks for nanotechnology.
机译：锁核酸(恢复)是由二环核苷酸O2和C4的原子在哪里通过亚甲基桥和糖有关被阻塞在3 ' endo构象。治疗和代表一个有前途的工具诊断应用程序和特点是更高的热稳定性和抗核酸酶对自然的同行。然而,结构的描述LNA-containing四倍的相当有限,因为很少有核磁共振模型报道文学。all-LNA-substituted派生模型quadruplex-forming序列5‘-TGGGT-3’介绍了精制1.7 ?高分辨率晶体分析显示普通的平行G-quadruplex安排终止在一个定义良好的胸腺嘧啶四分体3 '端。在模式揭示了LNA-specific特性溶剂分布。包装四倍的存在不对称单位。形成一个紧凑的高阶结构。这个新的组装说明一个可能的方式连续的四重的可以处理拥挤的细胞环境。分子有序结构的形成自组装是一种有效的策略来获得纳米结构,本研究可以打开方式LNA-based建筑的设计的一个新类块纳米技术。

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