title: X-ray analyses of hybrid duplexes between antisense oligonucleotides containing 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine and their target RNAs.
abstract: Incorporation of 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine ((N)Um) into oligonucleotides increases antisense properties such as RNA binding affinity, nuclease resistance and RNase H activity. The present X-ray studies on hybrid duplexes formed between antisense oligonucleotides containing (N)Um and their target RNAs have revealed the structural basis for such properties. The terminal ammonium groups of the aminohexyl chains interact with the phosphate oxygen anions. The 2'-O-methyl modification induces the ribose group to adopt the C3'-endo conformation. Comparisons with the structure of unmodified duplex show that the (N)Um incorporation narrows the minor grooves and alters their hydration structures. These structural changes are well correlated to the favorable properties for useful antisense molecules.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Ella Czarina Magat
authors.initials: EC
authors.lastname: Juan
authors.forename: Jiro
authors.initials: J
authors.lastname: Kondo
authors.forename: Takanori
authors.initials: T
authors.lastname: Ito
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ueno
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Akio
authors.initials: A
authors.lastname: Takénaka
mesh_terms: D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C474860:5-(N-aminohexyl)carbamoyl-2'-O-methyluridine; D020319:Oligodeoxyribonucleotides, Antisense; D012313:RNA; D014529:Uridine