The biological impact of sequence-specific DNA alkylation by pyrrole-imidazole polyamides.
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.
Sasaki
Shunta
S
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa Oiwake, Sakyo-ku, Kyoto 606-8502, Japan.
Minoshima
Masafumi
M
Shimizu
Tatsuhiko
T
Fujimoto
Jun
J
Shinohara
Ken-ichi
K
Bando
Toshikazu
T
Sugiyama
Hiroshi
H
D000478:Alkylation / Q000187:drug effects; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D020868:Gene Silencing / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000737:chemistry; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D018906:Antineoplastic Agents, Alkylating; D007211:Indoles; D009757:Nylons; D004247:DNA