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Sequence-specific gene silencing by alkylating Py-Im polyamide. 2005

Ken-ichi Shinohara, and Shunta Sasaki, and Toshikazu Bando, and Hiroshi Sugiyama
Graduate School of Science, Kyoto University, Kitashirakawa Oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.

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.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D009757 Nylons Polymers where the main polymer chain comprises recurring amide groups. These compounds are generally formed from combinations of diamines, diacids, and amino acids and yield fibers, sheeting, or extruded forms used in textiles, gels, filters, sutures, contact lenses, and other biomaterials. Polyamides,Dermalon,Ethilon,Nylon,Polyamide,Supramid,Dermalons,Ethilons,Supramids
D011758 Pyrroles Azoles of one NITROGEN and two double bonds that have aromatic chemical properties. Pyrrole
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000477 Alkylating Agents Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. Alkylating Agent,Alkylator,Alkylators,Agent, Alkylating,Agents, Alkylating
D000478 Alkylation The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. Alkylations
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049408 Luminescent Agents Compound such as LUMINESCENT PROTEINS that cause or emit light (PHYSICAL LUMINESCENCE). Phosphorescent Agents,Agents, Luminescent,Agents, Phosphorescent

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