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

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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-12, Vol.16 (24), p.6161-6164
Main Authors: Le, N. Minh, Sielaff, Alan M., Cooper, Amanda J., Mackay, Hilary, Brown, Toni, Kotecha, Minal, O’Hare, Caroline, Hochhauser, Daniel, Lee, Moses, Hartley, John A.
Format: Article
Language:English
Subjects:
Achiral
Antineoplastic agents
Biological and medical sciences
CC-1065
Dimer
Duocarmycins
Footprinting
Gene control
General aspects
Medical sciences
Pharmacology. Drug treatments
Polyamides
Pyrrolobenzodiazepines
sec-amino-CBI
Sequence specificity
SPR
Topoisomerase
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.09.043