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The biological impact of sequence-specific DNA alkylation by pyrrole-imidazole polyamides
Shunta Sasaki1, Masafumi Minoshima, Tatsuhiko Shimizu
1Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa Oiwake, Sakyo-ku, Kyoto 606-8502, Japan.
Abstract:
We have developed a series of novel DNA alkylating polyamides possessing indole linkers. Investigations using high-resolution gel electrophoresis revealed that the indole linked Py-Im polyamide alkylated at A of a targeted nine base pair matching sequence. Evaluation in human cancer cell lines revealed that the indole linked Py-Im polyamides have strong cytotoxicities. Furthermore, we showed that alkylation of the template strand of the coding region by these polyamides causes effective gene silencing.
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