Specific alkylation of human telomere repeats by hairpin pyrrole-imidazole polyamide

被引：17

作者：

Takahashi, R ^{[1
]}

Bando, T ^{[1
]}

Sugiyama, H ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Div Biofunct Mol, Tokyo 1010062, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2003年 / 11卷 / 12期

关键词：

D O I：

10.1016/S0968-0896(03)00176-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel hairpin polyamide-cyclopropapyrroloindole (CPI) conjugate PyImImIm-gamma-PyPyPyLDu86 (conjugate 11), which targets human telomere repeats d(TTAGGG)(n)/d(CCCTAA)(n), was synthesized. High resolution denaturing polyacrylamide gel electrophoresis using 44 bp DNA fragments and HPLC product analysis of a synthetic nonanucleotide demonstrated that conjugate 11 alkylates the target adenine in the telomere repeats, 5'-CCCTAA-3'. Examination of the antitumor activity of conjugate 11 using a panel of 39 cancer cell lines demonstrated that the average concentration of conjugate 11 required for 50% growth inhibition was 5.75 muM, which is superior to pepleomycin and bleomycin and comparable to cisplatin. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：2503 / 2509

页数：7

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