Takahashi Ryoko, Bando Toshikazu, Sugiyama Hiroshi
Division of Biofunctional Molecules, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Surugadai, Kanda, Chiyoda, Tokyo 101-0062, Japan.
Bioorg Med Chem. 2003 Jun 12;11(12):2503-9. doi: 10.1016/s0968-0896(03)00176-7.
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 microM, which is superior to pepleomycin and bleomycin and comparable to cisplatin.
合成了一种靶向人端粒重复序列d(TTAGGG)(n)/d(CCCTAA)(n)的新型发夹状聚酰胺-环丙基吡咯并吲哚（CPI）共轭物PyImImIm-γ-PyPyPyLDu86（共轭物11）。使用44 bp DNA片段进行的高分辨率变性聚丙烯酰胺凝胶电泳以及合成的九核苷酸的HPLC产物分析表明，共轭物11使端粒重复序列5'-CCCTAA-3'中的靶腺嘌呤烷基化。使用一组39种癌细胞系检测共轭物11的抗肿瘤活性表明，50%生长抑制所需的共轭物11的平均浓度为5.75 microM，优于培普利霉素和博来霉素，与顺铂相当。
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