title: X-ray analyses of DNA duplexes containing 5-(N-aminohexyl)carbamoyl modifications.
abstract: Oligonucleotides containing polyamines are currently being evaluated as potential antigene compounds for therapeutic purposes. Among them, 5-(N-aminohexyl) carbamoyl-2'-deoxyuridine ((N)U) and 5-(N-aminohexyl) carbamoyl-2'-O-methyluridine ((N)Um) substituted oligonucleotides have higher resistance against nuclease degradation compared to native DNA. Furthermore, oligonucleotides containing (N)U stabilizes duplex formation with the complementary DNA. To elucidate the mechanisms behind these improved antigene properties, we synthesized and crystallized two Dickerson-Drew-type DNA duplexes containing (N)U and (N)Um. The 2'-O-methyl modification in (N)Um was found to induce the ribose ring to adopt the C3'-endo conformation. Electron density maps show possible interactions of the terminal ammonium ion of the aminohexyl groups with the phosphate oxygen anions.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Ella Czarina Magat
authors.initials: EC
authors.lastname: Juan
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurihara
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; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry*; D012266:Ribose / Q000737:chemistry; D012399:Rotation; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C474860:5-(N-aminohexyl)carbamoyl-2'-O-methyluridine; C108707:5-(N-aminohexyl)carbamoyl-2'-deoxyuridine; D009692:Nucleic Acid Heteroduplexes; D012266:Ribose; D003857:Deoxyuridine; D014529:Uridine