title: Anti-HIV-1 activity of an antisense phosphorothioate oligonucleotide bearing imidazole and primary amine groups.
abstract: We have previously shown that RNA cleaving reagents with imidazole and primary amine groups on the 5'-end of antisense oligodeoxyribonucleotides could site-specifically cleave CpA as the target sequence of the substrate tRNA in vitro. In this study, a RNA cleaving reagent, composed of imidazole and primary amine groups on an antisense phosphorothioate oligonucleotide (Im-anti-s-ODN), was synthesized and evaluated for anti-HIV-1 activity in MT-4 cells. The sequence of the Im-anti-s-ODN was designed to be complementary to the HIV-1 gag-mRNA and to bind adjacent to the CpA cleavage site position. Im-anti-s-ODN encapsulated with the transfection reagent, DMRIE-C, had higher anti-HIV-1 activity than the unmodified antisense phosphorothioate oligonucleotide (anti-s-ODN) at a 2 microM concentration. Furthermore, the Im-anti-ODN encapsulated with DMRIE-C conferred sequence-specific inhibition.
authors.affiliation: Department of Industrial Chemistry, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ushijima
authors.forename: M
authors.initials: M
authors.lastname: Shirakawa
authors.forename: K
authors.initials: K
authors.lastname: Kagoshima
authors.forename: W S
authors.initials: WS
authors.lastname: Park
authors.forename: N
authors.initials: N
authors.lastname: Miyano-Kurosaki
authors.forename: H
authors.initials: H
authors.lastname: Takaku
mesh_terms: D000588:Amines / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000588:Amines; D019380:Anti-HIV Agents; D007093:Imidazoles; D016376:Oligonucleotides, Antisense; C029899:imidazole