Synthesis of Oligodiaminosaccharides Having α-Glycoside Bonds and Their Interactions with Oligonucleotide Duplexes
Synthesis of Oligodiaminosaccharides Having α-Glycoside Bonds and Their Interactions with Oligonucleotide Duplexes
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DOI：
10.1021/jo200951p
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发表时间：
2011-08-05
影响因子：
3.6
通讯作者：
Wada, Takeshi
中科院分区：
文献类型：
--
作者：
Iwata, Rintaro;Sudo, Masafumi;Wada, Takeshi
本发明描述了新的寡二氨基糖，α-（1 -> 4）连接的-2，6-二氨基-2，6-二脱氧-D-吡喃葡萄糖寡聚物的合成及其与核酸双链体DNA-DNA、RNA-RNA和DNA-RNA的相互作用。使用包括6-邻苯二甲酰亚胺糖基供体的糖基化反应的链延长循环，成功地合成了具有α-糖基键的低聚二氨基葡萄糖衍生物的单体至四聚体。在寡二氨基糖不存在和存在的情况下，对各种核酸双链体进行UV熔解实验。合成的寡二氨基糖对A型RNA-RNA和DNA-RNA双链体具有显著的热力学稳定作用，而对B型DNA-DNA双链体则没有稳定作用。在寡二氨基糖中，四聚体表现出最高的稳定A型双链体的能力，并且由四聚体诱导的T（m）值的增加高于由新霉素B和妥布霉素诱导的T（m）值的增加，新霉素B和妥布霉素是已知的具有结合和稳定多种RNA分子的能力的氨基糖苷类。CD光谱实验表明，低聚二氨基糖引起小的结构变化的RNA-RNA双链体，而没有观察到明显的变化，在DNA-DNA双链体的结构。ITC（等温滴定量热法）实验表明，RNA-RNA双链体与四二氨基糖之间相互作用产生的热量大约是DNA-DNA双链体与四二氨基糖之间相互作用产生的热量的两倍。这些结果有力地表明，存在一个A型核酸特异性结合模式的寡二氨基糖，结合这些双链体，并导致小的结构变化。
Syntheses of the novel oligodiaminosaccharides, alpha-(1 -> 4)linked-2,6-diamino-2,6-dideoxy-D-glucopyranose oligomers, and their interactions with nucleic acid duplexes DNA-DNA, RNA-RNA, and DNA-RNA are described. Monomers to tetramers of oligodiaminoglucose derivatives having alpha-glycosyl bonds were successfully synthesized using a chain elongation cycle including glycosylation reactions of a 6-phthalimide glycosyl donor. UV melting experiments for a variety of nucleic acid duplexes in the absence and presence of the oligodiaminosaccharides were performed. The synthesized oligodiaminosaccharides exhibited notable thermodynamic stabilization effects on A-type RNA-RNA and DNA-RNA duplexes, whereas B-type DNA-DNA duplexes were not stabilized by the synthesized oligodiaminosaccharides. Among the oligodiaminosaccharides, the tetramer exhibited the highest ability to stabilize A-type duplexes, and the increase in T(m) values induced by the tetramer were higher than those induced by neomycin B and tobramycin, which are known aminoglycosides having ability to bind and stabilize a variety of RNA molecules. CD spectrometry experiments revealed that the oligodiaminosaccharides caused small structural changes in RNA-RNA duplexes, whereas no appreciable changes were observed in the structure of DNA-DNA duplexes. ITC (isothermal titration calorimetry) experiments demonstrated that the amount of heat generated by the interaction between RNA-RNA duplexes and the tetradiaminosaccharides was approximately double that generated by that between DNA-DNA duplexes and the tetradiaminosaccharides. These results strongly suggested the existence of an A-type nucleic acid specific-binding mode of the oligodiaminosaccharides, which bind to these duplexes and cause small structural changes.