title: Synthesis of oligodiaminosaccharides having α-glycoside bonds and their interactions with oligonucleotide duplexes.
abstract: 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.
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
authors.forename: Rintaro
authors.initials: R
authors.lastname: Iwata
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sudo
authors.forename: Kenta
authors.initials: K
authors.lastname: Nagafuji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry*; D001483:Base Sequence; D002151:Calorimetry; D004247:DNA / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry*; D011485:Protein Binding; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000617:Aminoglycosides; D006027:Glycosides; D009841:Oligonucleotides; D009844:Oligosaccharides; D012313:RNA; D004247:DNA