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Nucleic Acids Research 2006 34(4):1189-1195; doi:10.1093/nar/gkl005
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Published online 25 February 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

Alkylation of template strand of coding region causes effective gene silencing

Ken-ichi Shinohara, Shunta Sasaki, Masafumi Minoshima, Toshikazu Bando and Hiroshi Sugiyama*

Department of Chemistry, Graduate School of Science, Kyoto University Kitashirakawa-Oiwakecho, Sakyo, Kyoto, 606-8502, Japan

*To whom correspondence should be addressed. Tel: +81 75 753 4002; Fax: +81 75 753 3670; Email: hs{at}kuchem.kyoto-u.ac.jp

Received January 30, 2006. Revised February 10, 2006. Accepted February 10, 2006.

We recently developed a new type of pyrrole (Py)–imidazole (Im) polyamide–tetrahydrocyclopropabenzindolone (CBI) conjugate with an indole linker as a stable sequence-specific alkylating agent. In this study, we investigated the gene silencing activities of polyamides A, B and C, which selectively alkylate specific sequences in the promoter region, non-coding strand and coding strand, respectively, of the green fluorescent protein (GFP) gene. GFP vectors were transfected into human colon carcinoma cells (HCT116), and the cells were treated with 100 nM of the polyamides for 24 h. Fluorescence microscopy indicated that a significant reduction of GFP fluorescence was only observed in the cells that were treated with polyamide C. In clear contrast, polyamides A and B did not show such activity. Moreover, real-time PCR demonstrated selective reduction of the expression of GFP mRNA following treatment with polyamide C. These results suggest that alkylating Py–Im polyamides that target the coding strand represent a novel approach for sequence-specific gene silencing.


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