Abstract Chemically modified oligonucleotides (ONs) have recently gained much attention as therapeutic materials because of their improved properties. Here, a newly designed nucleic acid analog based on α-l-threosamine (named cTNA) is reported. cTNA has a “dual” constrained structure, with a bridged sugar moiety and shorter phosphoramidate backbone, to reduce the entropy loss during the hybridization. Unexpectedly, ONs containing the cTNA unit showed lower binding affinity with complementary RNA and DNA than natural ONs. Quantum chemical calculations imply that the relative nucleobase orientation of cTNA may be unfavorable for hybridization.

中文翻译：

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基于 α-l-苏糖胺的高度受限的核酸类似物

摘要 化学修饰的寡核苷酸（ONs）由于其改进的特性，最近作为治疗材料受到了广泛关注。在这里，报道了一种新设计的基于 α-l-苏糖胺（命名为 cTNA）的核酸类似物。cTNA 具有“双重”约束结构，具有桥接糖部分和较短的氨基磷酸酯骨架，以减少杂交过程中的熵损失。出乎意料的是，与天然 ON 相比，含有 cTNA 单元的 ON 与互补 RNA 和 DNA 的结合亲和力较低。量子化学计算表明 cTNA 的相对核碱基方向可能不利于杂交。