Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 IIalpha 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 IIalpha 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.
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PMID:Binding of f-PIP, a pyrrole- and imidazole-containing triamide, to the inverted CCAAT box-2 of the topoisomerase IIalpha promoter and modulation of gene expression in cells. 1701 Nov 87

The synthesis, DNA binding characteristics and biological activity of an N-formamido pyrrole- and imidazole-containing H-pin polyamide (f-PIP H-pin, 2) designed to selectively target the ICB2 site on the topoIIalpha promoter, is reported herein. Thermal denaturation, circular dichroism, isothermal titration calorimetry, surface plasmon resonance and DNase I footprinting studies demonstrated that 2 maintained the selectivity of the unlinked parent monomer f-PIP (1) and with a slight enhancement in binding affinity (K(eq)=5 x 10(5)M(-1)) to the cognate site (5'-TACGAT-3'). H-pin 2 also exhibited comparable ability to inhibit NF-Y binding to 1, as demonstrated by gel shift studies. However, in stark contrast to monomer 1, the H-pin did not affect the up-regulation of topoisomerase IIalpha (topoIIalpha) in cells (Western blot), suggesting that the H-pin does not enter the nucleus. This study is the first to the authors' knowledge that reports such a markedly different cellular response between two compounds of almost identical binding characteristics.
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PMID:Targeting the ICB2 site of the topoisomerase IIalpha promoter with a formamido-pyrrole-imidazole-pyrrole H-pin polyamide. 2061 12