Synthesis of oligodiaminomannoses and analysis of their RNA duplex binding properties and their potential application as siRNA-based drugs

Synthesis of oligodiaminomannoses and analysis of their RNA duplex binding properties and their potential application as siRNA-based drugs
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寡二氨基甘露糖的合成及其 RNA 双链体结合特性的分析及其作为 siRNA 药物的潜在应用

DOI:
10.1039/c5ob01384d
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发表时间:
2015
影响因子:
3.2
通讯作者:
T.
T.
中科院分区:
化学3区
文献类型:
--
作者:
Iwata;R; Doi;A.; Maeda;Y.; Wada;T.

文献摘要

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描述了人工阳离子低聚二氨基糖、α-(1 → 4)-连接-2,6-二氨基-2,6-二脱氧-D-吡喃甘露糖低聚物 (ODAMan) 的合成及其与 RNA 双链体的相互作用。成功制备了单体到五聚体,所有这些都带有非天然的2,6-二氨基甘露糖部分。 UV 熔解和荧光各向异性分析表明,ODAMan 结合并热力学稳定了 12mer RNA 双链体和 siRNA。此外,清楚地表明,siRNA 由于与 ODAMan 4mer 结合而获得了显着的 RNase A 抗性。
The synthesis of artificial cationic oligodiaminosaccharides, α-(1 → 4)-linked-2,6-diamino-2,6-dideoxy-D-mannopyranose oligomers (ODAMans), and their interactions with RNA duplexes are described. The monomer through the pentamer, all of which bear unnatural 2,6-diaminomannose moieties, were successfully prepared. UV melting and fluorescence anisotropy analyses revealed that the ODAMans bound and thermodynamically stabilized both 12mer RNA duplexes and an siRNA. Furthermore, it was clearly shown that the siRNA acquired substantial RNase A resistance due to its binding to the ODAMan 4mer.