Synthesis of oligodiaminosaccharides having α-glycoside bonds and their interactions with oligonucleotide duplexes.

Syntheses of the novel oligodiaminosaccharides, α-(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 α-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.

Stabilization of A-type nucleic acid duplexes by novel oligodiaminosaccharides.

Novel oligodiaminosaccharides, alpha-(1-->4)-linked-2,6-diamino-2,6-dideoxy-D-glucopyranose oligomers, were designed and synthesized to bind to A-type nucleic acid duplexes, such as RNA duplexes. Using properly designed glycosyl donors and glycosyl acceptors, an alpha-selective glycosylation was achieved. A chain elongation cycle was established and the oligodiaminosaccharides bearing the alpha-glycoside bonds (1-4mer) were synthesised. Analyses of their interactions with oligonucleotide duplexes were performed by using CD spectrometry and UV melting experiments. These experiments revealed that the 3mer and 4mer were found to remarkably stabilize RNA-RNA and RNA-DNA duplexes with small structural changes.