Binding of f-PIP, a pyrrole- and imidazole-containing triamide, to the inverted CCAAT box-2 of the topoisomerase IIα promoter and modulation of gene expression in cells
- 作者：N. Minh Le ; Alan M. Sielaff ; Am ; a J. Cooper ; Hilary Mackay ; Toni Brown ; Minal Kotecha ; Caroline O’ ; Hare ; Daniel Hochhauser ; Moses Lee ; John A. Hartley
- 关键词：CC-1065 ; Duocarmycins ; Pyrrolobenzodiazepines ; Achiral ; sec-amino-CBI ; Dimer ; Polyamides ; Sequence specificity ; Footprinting ; SPR ; Gene control ; Topoisomerase
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2006
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：15 December 2006
- 卷：16
- 期：24
- 页码：6161-6164
- 文件大小：314 K
摘要
An N-formamido pyrrole- and imidazole-containing triamide (f-PIP) has been shown by DNase I footprinting, SPR, and CD studies to bind as a stacked dimer to its cognate sequences: 5′-TACGAT-3′ (5′-flank of the inverted CCAAT box-2 of the human topoisomerase IIα promoter) and 5′-ATCGAT-3′. A gel shift experiment provided evidence for f-PIP to inhibit protein–DNA interaction at the ICB2 site. Western blot studies showed that expression of the topoisomerase IIα gene in confluent NIH 3T3 cells was induced by treatment with f-PIP. The results suggested that the triamide was able to enter the nucleus, interacted with the target site within ICB2, inhibited NF-Y binding, and activated gene expression.