DNA alkylation by pyrrole-imidazole seco-CBI conjugates with an indole linker:: Sequence-specific DNA alkylation with 10-base-pair recognition through heterodimer formation

被引：41

作者：

Minoshima, Masafumi ^{[1
]}

Bando, Toshikazu ^{[1
]}

Sasaki, Shunta ^{[1
]}

Shinohara, Ken-ichi ^{[1
]}

Shimizu, Tatsuhiko ^{[1
]}

Fujimoto, Jun ^{[1
]}

Sugiyama, Hiroshi ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Sci, Dept Chem, Kyoto 6068502, Japan

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2007年 / 129卷 / 17期

关键词：

D O I：

10.1021/ja065235a

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The sequence-specific DNA alkylation by conjugates 4 and 5 which consist of N-methylpyrrole (Py)-N-methylimidazole (lm) polyamides and 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) linked with an indole linker, was investigated in the absence of presence of partner Py-Im polyamide 6. High-resolution denaturing polyacrylamide gel electrophoresis revealed that conjugate 4 alkylates DNA at the sequences 5'-(A/T)GCCTA-3' through hairpin formation, and alkylates 5'-GGAAA-GAAAA-3' through an extended binding mode. However, in the presence of partner Py-Im polyamide 6, conjugate 4 alkylates DNA at a completely different sequence, 5'AGGTTGTCCA-3'. Alkylation of 4 in the presence of 6 was effectivley inhibited by competitor 7. Surface plasmon resonances (SPR) results indicated that conjugate 4 does not bind to 5'-AGGTTGTCCA-3', whereas 6 binds tightly to htis sequence. The results suggest that alkylation proceeds through heterodimer formation, indicating that this is a general way to expand the recognition sequence for DNA alkylation by Py-Im seco CBI conjugates.

引用

页码：5384 / 5390

页数：7

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