title: Sequence-specific gene silencing by alkylating Py-Im polyamide.
abstract: We have demonstrated that hairpin pyrrole (Py)-imidazole (Im) polyamide-CPI conjugates selectively induced luciferase gene silencing by sequence-specific alkylation of the coding region. Recently, we developed a new type of Py-Im polyamide CBI conjugate with an indole linker as a stable sequence-specific alkylating agent. In this study, we investigated the gene silencing ability of polyamides A, B and C, which potentially target specific sequences in the promoter region, non-coding strand, and coding strand of the green fluorescent protein (GFP) gene, respectively. The GFP vectors were transfected into human colon carcinoma cells (HCT116), and the cells treated with 100 nM of the polyamides for 24 h. Using direct observation of cell by fluorescence microscopy, a significant GFP-gene silencing effect was only seen with treatment with polyamide C. Polyamides A and B did not show such activity.
authors.affiliation: Graduate School of Science, Kyoto University, Kitashirakawa Oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Shinohara
authors.forename: Shunta
authors.initials: S
authors.lastname: Sasaki
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry* / Q000494:pharmacology*; D000478:Alkylation; D001483:Base Sequence; D045744:Cell Line, Tumor; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D049408:Luminescent Agents; D008856:Microscopy, Fluorescence; D009757:Nylons / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry*
chemical_list: D000477:Alkylating Agents; D007093:Imidazoles; D049408:Luminescent Agents; D009757:Nylons; D011758:Pyrroles; D049452:Green Fluorescent Proteins