具有序列特异性DNA烷基化部分的发夹型吡咯-咪唑聚酰胺的分子设计。

Molecular design of hairpin pyrrole-imidazole polyamides possessing sequence specific DNA alkylating moiety.

作者信息

Narita Akihiko, Bando Toshikazu, Sugiyama Hiroshi

机构信息

School of Biomedical Science, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.

出版信息

Nucleic Acids Res Suppl. 2003(3):119-20. doi: 10.1093/nass/3.1.119.

DOI:10.1093/nass/3.1.119

PMID:14510409

Abstract

By conjugating pyrrole (Py)/imidazole (Im) hairpin polyamides with CBI, a stable alkylating moiety, we have developed a new type of DNA-sequence-specific alkylating agent. The sequence specificity and alkylation efficiency of the CBI conjugates were analyzed with high-resolution denaturing gel electrophoresis using linear 450- and 1000-bp DNA. The results demonstrate that CBI conjugates selectively alkylate adenine in specific sequences, whereas the previous type of alkylating polyamide, which contains segment A of DU-86, alkylates both adenine and guanine.

摘要

通过将吡咯（Py）/咪唑（Im）发夹型聚酰胺与稳定的烷基化部分CBI共轭，我们开发了一种新型的DNA序列特异性烷基化剂。使用线性450和1000碱基对的DNA，通过高分辨率变性凝胶电泳分析了CBI共轭物的序列特异性和烷基化效率。结果表明，CBI共轭物在特定序列中选择性地使腺嘌呤烷基化，而先前类型的烷基化聚酰胺（其包含DU-86的A片段）则使腺嘌呤和鸟嘌呤都烷基化。