Sequence-Specific Gene Silencing in Mammalian Cells by Alkylating Pyrrole−Imidazole Polyamides
Gene silencing was examined by sequence-specific alkylation of DNA by N-methylpyrrole (Py)-N-methylimidazole (Im) hairpin polyamides. Polyamides ImImPyPyγImImPyLDu86 (A) and ImImPyPyγImPyPyLDu86 (B) selectively alkylated the coding regions of the renilla and firefly luciferases, respectively, accord...
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| Veröffentlicht in: | Journal of the American Chemical Society 2004-04, Vol.126 (16), p.5113-5118 |
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| container_title | Journal of the American Chemical Society |
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| creator | Shinohara, Ken-ichi Narita, Akihiko Oyoshi, Takanori Bando, Toshikazu Teraoka, Hirobumi Sugiyama, Hiroshi |
| description | Gene silencing was examined by sequence-specific alkylation of DNA by N-methylpyrrole (Py)-N-methylimidazole (Im) hairpin polyamides. Polyamides ImImPyPyγImImPyLDu86 (A) and ImImPyPyγImPyPyLDu86 (B) selectively alkylated the coding regions of the renilla and firefly luciferases, respectively, according to the base pair recognition rule of Py−Im polyamides. Two different plasmids, encoding renilla luciferase and firefly luciferase, were used as vectors to examine the effect of alkylation on gene silencing. Transfection of the alkylated luciferase vectors-by polyamide A or B-into HeLa, 293, and NIH3T3 cells demonstrated that these sequence-specific DNA alkylations lead to selective silencing of gene expression. Next, the vectors were cotransfected into HeLa cells and the cells were treated with polyamide A or B. Selective reduction of luciferase activities was caused by both polyamides. On the basis of this sequence-specific alkylation and gene silencing activity, these alkylating Py−Im polyamides thus have potential as antitumor drugs to target specific gene expression in human cells. |
| doi_str_mv | 10.1021/ja031673v |
| format | Article |
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Polyamides ImImPyPyγImImPyLDu86 (A) and ImImPyPyγImPyPyLDu86 (B) selectively alkylated the coding regions of the renilla and firefly luciferases, respectively, according to the base pair recognition rule of Py−Im polyamides. Two different plasmids, encoding renilla luciferase and firefly luciferase, were used as vectors to examine the effect of alkylation on gene silencing. Transfection of the alkylated luciferase vectors-by polyamide A or B-into HeLa, 293, and NIH3T3 cells demonstrated that these sequence-specific DNA alkylations lead to selective silencing of gene expression. Next, the vectors were cotransfected into HeLa cells and the cells were treated with polyamide A or B. Selective reduction of luciferase activities was caused by both polyamides. On the basis of this sequence-specific alkylation and gene silencing activity, these alkylating Py−Im polyamides thus have potential as antitumor drugs to target specific gene expression in human cells.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/ja031673v</identifier><identifier>PMID: 15099094</identifier><identifier>CODEN: JACSAT</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Alkylation ; Animals ; Base Sequence ; Biological and medical sciences ; Cells, Cultured ; DNA - chemistry ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Silencing ; HeLa Cells ; Humans ; Imidazoles - chemistry ; Luciferases - chemistry ; Luciferases - genetics ; Mice ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; Molecular Structure ; NIH 3T3 Cells ; Nucleic Acid Conformation ; Nylons - chemistry ; Pyrroles - chemistry</subject><ispartof>Journal of the American Chemical Society, 2004-04, Vol.126 (16), p.5113-5118</ispartof><rights>Copyright © 2004 American Chemical Society</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a379t-f2902b708b48aee47986eac0b5d8fe776ebb33dbb5ad70467cec9162b42789443</citedby><cites>FETCH-LOGICAL-a379t-f2902b708b48aee47986eac0b5d8fe776ebb33dbb5ad70467cec9162b42789443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ja031673v$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ja031673v$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27078,27926,27927,56740,56790</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15732664$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15099094$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shinohara, Ken-ichi</creatorcontrib><creatorcontrib>Narita, Akihiko</creatorcontrib><creatorcontrib>Oyoshi, Takanori</creatorcontrib><creatorcontrib>Bando, Toshikazu</creatorcontrib><creatorcontrib>Teraoka, Hirobumi</creatorcontrib><creatorcontrib>Sugiyama, Hiroshi</creatorcontrib><title>Sequence-Specific Gene Silencing in Mammalian Cells by Alkylating Pyrrole−Imidazole Polyamides</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>Gene silencing was examined by sequence-specific alkylation of DNA by N-methylpyrrole (Py)-N-methylimidazole (Im) hairpin polyamides. Polyamides ImImPyPyγImImPyLDu86 (A) and ImImPyPyγImPyPyLDu86 (B) selectively alkylated the coding regions of the renilla and firefly luciferases, respectively, according to the base pair recognition rule of Py−Im polyamides. Two different plasmids, encoding renilla luciferase and firefly luciferase, were used as vectors to examine the effect of alkylation on gene silencing. Transfection of the alkylated luciferase vectors-by polyamide A or B-into HeLa, 293, and NIH3T3 cells demonstrated that these sequence-specific DNA alkylations lead to selective silencing of gene expression. Next, the vectors were cotransfected into HeLa cells and the cells were treated with polyamide A or B. Selective reduction of luciferase activities was caused by both polyamides. On the basis of this sequence-specific alkylation and gene silencing activity, these alkylating Py−Im polyamides thus have potential as antitumor drugs to target specific gene expression in human cells.</description><subject>Alkylation</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>DNA - chemistry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Silencing</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Imidazoles - chemistry</subject><subject>Luciferases - chemistry</subject><subject>Luciferases - genetics</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>Molecular Structure</subject><subject>NIH 3T3 Cells</subject><subject>Nucleic Acid Conformation</subject><subject>Nylons - chemistry</subject><subject>Pyrroles - chemistry</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkM-O0zAQhy0EYsvCgRdAuYDEIeB_sZPjqoJlRREVXUDiYsbOBLnrJF27RYQn4Mwj8iS4arXLgZM9nk8_z3yEPGb0BaOcvVwDFUxp8f0OmbGK07JiXN0lM0opL3WtxAl5kNI6l5LX7D45YRVtGtrIGfm6wusdDg7L1Qad77wrznHAYuVDfvXDt8IPxTvoewgehmKOIaTCTsVZuJoCbPfAcopxDPjn1--L3rfwM9-L5RgmyBWmh-ReByHho-N5Sj6-fnU5f1Mu3p9fzM8WJQjdbMuON5RbTWsra0CUuqkVgqO2ausOtVZorRCttRW0mkqlHbqGKW4l13UjpTglzw65mzjmjdLW9D65PC4MOO6S0ayumNQig88PoItjShE7s4m-hzgZRs1ep7nRmdknx9Cd7bG9JY_-MvD0CEByELoIWVr6h9OCK7XnygPn0xZ_3PQhXpn8ka7M5XJlvrxdaPah-Ww-3eaCS2Y97uKQ3f1nwL8qBZl-</recordid><startdate>20040428</startdate><enddate>20040428</enddate><creator>Shinohara, Ken-ichi</creator><creator>Narita, Akihiko</creator><creator>Oyoshi, Takanori</creator><creator>Bando, Toshikazu</creator><creator>Teraoka, Hirobumi</creator><creator>Sugiyama, Hiroshi</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040428</creationdate><title>Sequence-Specific Gene Silencing in Mammalian Cells by Alkylating Pyrrole−Imidazole Polyamides</title><author>Shinohara, Ken-ichi ; Narita, Akihiko ; Oyoshi, Takanori ; Bando, Toshikazu ; Teraoka, Hirobumi ; Sugiyama, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a379t-f2902b708b48aee47986eac0b5d8fe776ebb33dbb5ad70467cec9162b42789443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Alkylation</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>DNA - chemistry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Silencing</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Imidazoles - chemistry</topic><topic>Luciferases - chemistry</topic><topic>Luciferases - genetics</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>Molecular Structure</topic><topic>NIH 3T3 Cells</topic><topic>Nucleic Acid Conformation</topic><topic>Nylons - chemistry</topic><topic>Pyrroles - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shinohara, Ken-ichi</creatorcontrib><creatorcontrib>Narita, Akihiko</creatorcontrib><creatorcontrib>Oyoshi, Takanori</creatorcontrib><creatorcontrib>Bando, Toshikazu</creatorcontrib><creatorcontrib>Teraoka, Hirobumi</creatorcontrib><creatorcontrib>Sugiyama, Hiroshi</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shinohara, Ken-ichi</au><au>Narita, Akihiko</au><au>Oyoshi, Takanori</au><au>Bando, Toshikazu</au><au>Teraoka, Hirobumi</au><au>Sugiyama, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sequence-Specific Gene Silencing in Mammalian Cells by Alkylating Pyrrole−Imidazole Polyamides</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2004-04-28</date><risdate>2004</risdate><volume>126</volume><issue>16</issue><spage>5113</spage><epage>5118</epage><pages>5113-5118</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><coden>JACSAT</coden><abstract>Gene silencing was examined by sequence-specific alkylation of DNA by N-methylpyrrole (Py)-N-methylimidazole (Im) hairpin polyamides. Polyamides ImImPyPyγImImPyLDu86 (A) and ImImPyPyγImPyPyLDu86 (B) selectively alkylated the coding regions of the renilla and firefly luciferases, respectively, according to the base pair recognition rule of Py−Im polyamides. Two different plasmids, encoding renilla luciferase and firefly luciferase, were used as vectors to examine the effect of alkylation on gene silencing. Transfection of the alkylated luciferase vectors-by polyamide A or B-into HeLa, 293, and NIH3T3 cells demonstrated that these sequence-specific DNA alkylations lead to selective silencing of gene expression. Next, the vectors were cotransfected into HeLa cells and the cells were treated with polyamide A or B. Selective reduction of luciferase activities was caused by both polyamides. On the basis of this sequence-specific alkylation and gene silencing activity, these alkylating Py−Im polyamides thus have potential as antitumor drugs to target specific gene expression in human cells.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>15099094</pmid><doi>10.1021/ja031673v</doi><tpages>6</tpages></addata></record> |
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| subjects | Alkylation Animals Base Sequence Biological and medical sciences Cells, Cultured DNA - chemistry Fundamental and applied biological sciences. Psychology Gene Expression Gene Silencing HeLa Cells Humans Imidazoles - chemistry Luciferases - chemistry Luciferases - genetics Mice Molecular and cellular biology Molecular genetics Molecular Sequence Data Molecular Structure NIH 3T3 Cells Nucleic Acid Conformation Nylons - chemistry Pyrroles - chemistry |
| title | Sequence-Specific Gene Silencing in Mammalian Cells by Alkylating Pyrrole−Imidazole Polyamides |
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