基于异三聚体设计的具有11个碱基对识别能力的PI聚酰胺对双链人类端粒重复序列的协同烷基化作用。

Cooperative alkylation of double-strand human telomere repeat sequences by PI polyamides with 11-base-pair recognition based on a heterotrimeric design.

作者信息

Kashiwazaki Gengo, Bando Toshikazu, Shinohara Ken-ichi, Minoshima Masafumi, Nishijima Shigeki, Sugiyama Hiroshi

机构信息

Department of Chemistry, Graduate School of Science, and, Institute for integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8502, Japan.

出版信息

Bioorg Med Chem. 2009 Feb 1;17(3):1393-7. doi: 10.1016/j.bmc.2008.12.019. Epub 2008 Dec 24.

DOI:10.1016/j.bmc.2008.12.019

PMID:19124249

Abstract

We designed and synthesized alkylating conjugates 5-7 and their partner N-methylpyrrole-N-methylimidazole (PI) polyamides 8, 9. The DNA alkylating activities of conjugates 5-7 were evaluated by high-resolution denaturing polyacrylamide gel electrophoresis with a 219 base pair (bp) DNA fragment containing the human telomere repeat sequence. Conjugate 5 efficiently alkylated the sequence, 5'-GGTTAGGGTTA-3', in the presence of partner PI polyamide 8 or distamycin A (Dist). In contrast, the heterodimer system of 5 with 9 showed very weak alkylating activity. Accordingly, this heterotrimeric system of 5 with two short partners is an expedient way to attain improved precision and extension of the recognition of DNA sequences.

摘要

我们设计并合成了烷基化缀合物5 - 7及其对应的N - 甲基吡咯 - N - 甲基咪唑（PI）聚酰胺8、9。通过高分辨率变性聚丙烯酰胺凝胶电泳，使用包含人端粒重复序列的219个碱基对（bp）的DNA片段，评估缀合物5 - 7的DNA烷基化活性。在存在对应的PI聚酰胺8或distamycin A（Dist）的情况下，缀合物5能有效地烷基化序列5'-GGTTAGGGTTA-3'。相比之下，5与9的异二聚体系统显示出非常弱的烷基化活性。因此，5与两个短配体的这种异三聚体系统是提高DNA序列识别精度和扩展识别范围的便捷方法。