Sequence-specific alkylation of double-strand human telomere repeat sequence by pyrrole-imidazole polyamides with indole linkers

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作者
Sasaki, Shunta [1 ]
Bando, Toshikazu [1 ]
Minoshima, Masafumi [1 ]
Shimizu, Tatsuhiko [1 ]
Shinohara, Ken-Ichi [1 ]
Takaoka, Toshiyasu [1 ]
Sugiyama, Hiroshi [1 ]
机构
[1] Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto, 606-8502, Japan
来源
Journal of the American Chemical Society | 2006年 / 128卷 / 37期
关键词
We designed and synthesized pyrrole (Py)-imidazole (Im) hairpin polyamide 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) conjugates 1 and 2, which target both strands of -the double-stranded region of the human telomere repeat sequences, 5′-d(TTAGGG)n-3′/5′- d(CCCTAA)n-3′. High-resolution denaturing polyacrylamide gel electrophoresis demonstrated that conjugates 1 and 2 alkylated DNA at the 3′ A of 5′-ACCCTA-3′ and 5′-AGGGTTA-3′, respectively. Cytotoxicities of conjugates 1 and 2 were evaluated using 39 human cancer cell lines; averages of log IC50 values for conjugates 1 and 2 were -6.96 (110 nM) and -7.24 (57.5 nM); respectively. Conjugates 1 and 2 have potential as antitumor drugs capable of targeting telomere repeat sequence. © 2006 American Chemical Society;
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页码:12162 / 12168
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