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

被引：30

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] Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2006年 / 128卷 / 37期

关键词：

D O I：

10.1021/ja0626584

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：12162 / 12168

页数：7

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