吡咯-咪唑CBI缀合物对腺嘌呤的特异性烷基化作用。

Specific adenine alkylation by pyrrole-imidazole CBI conjugates.

作者信息

Bando Toshikazu, Narita Akihiko, Sasaki Shunta, Sugiyama Hiroshi

机构信息

Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto, 606-8502, Japan.

出版信息

J Am Chem Soc. 2005 Oct 12;127(40):13890-5. doi: 10.1021/ja052412j.

DOI:10.1021/ja052412j

PMID:16201810

Abstract

We examined DNA alkylation by pyrrole (Py)-imidazole (Im) hairpin polyamides, which possess 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) or cyclopropapyrroloindole (CPI) as DNA alkylating moieties. High-resolution denaturing gel electrophoresis revealed that alkylation by CBI conjugates 2 and 4 occurred specifically at adenines (A) in matched sequences, whereas CPI conjugates 1 and 3 alkylated both A and guanines (G) in matched sequences. The origin of the different reactivity of CBI and CPI conjugates is discussed in relation to the electrophilicity of the cyclopropane moiety. The high selectivity of the CBI conjugate gives additional sequence specificity relative to CPI conjugates that would be useful for the biological applications.

摘要

我们研究了以1,2,9,9a-四氢环丙并[1,2-c]苯并[1,2-e]吲哚-4-酮（CBI）或环丙并吡咯吲哚（CPI）作为DNA烷基化部分的吡咯（Py）-咪唑（Im）发夹型聚酰胺对DNA的烷基化作用。高分辨率变性凝胶电泳显示，CBI缀合物2和4的烷基化作用在匹配序列的腺嘌呤（A）处特异性发生，而CPI缀合物1和3在匹配序列中对腺嘌呤（A）和鸟嘌呤（G）均进行了烷基化。结合环丙烷部分的亲电性讨论了CBI和CPI缀合物不同反应性的起源。相对于CPI缀合物，CBI缀合物的高选择性提供了额外的序列特异性，这对于生物学应用将是有用的。