title: Synthesis of the antisense oligonucleotides carrying the modified 2-5A molecules at their 5'-termini and their properties.
abstract: The synthesis of 8-methyladenosine (1)-substituted 2-5A tetramers with hydroxyalkyl groups at the 5'-phosphates and the corresponding 2-5A-antisense chimeras is described. These oligonucleotides were synthesized by the phosphoramidite method with a DNA/RNA synthesizer. These 2-5A tetramers, 8 and 9, with hydroxyethyl and hydroxybutyl groups at their 5'-phosphates were more resistant to hydrolysis by alkaline phosphatase than those without the hydroxyalkyl groups. Incorporation of the hydroxyethyl group into the 2-5A tetramer and 2-5A-antisense chimera slightly reduced the abilities of their analogs to activate recombinant human RNase L, but the abilities of the 2-5A tetramer, 11, and the 2-5A-antisense chimera, 15, with the hydroxyethyl group and 1 returned to 80 and 50% relative to those of the un-modified oligonucleotides, 7 and 12, respectively. Furthermore, the enzyme activated by 2-5A-antisense chimera 15 cleaved the complementary RNA as efficiently as that activated by 2-5A-antisense chimera 12 without the hydroxyethyl group and 1. Thus, the 2-5A-antisense chimera carrying the hydroxyethyl group and 1 was found to be a good candidate for an antisense molecule.
authors.affiliation: Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ueno
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Shusaku
authors.initials: S
authors.lastname: Okatani
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kitade
mesh_terms: D000227:Adenine Nucleotides / Q000235:genetics*; D001483:Base Sequence; D004722:Endoribonucleases / Q000235:genetics; D006801:Humans; D006868:Hydrolysis; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry; D009843:Oligoribonucleotides / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics
chemical_list: D000227:Adenine Nucleotides; D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides; D011994:Recombinant Proteins; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease