Differential inhibition of various deoxyribonucleic acid polymerases by Evans blue and aurintricarboxylic acid.
The inhibitory effects of two anionic compounds, Evans blue and aurintricarboxylic acid (ATA), on various kinds of polynucleotide-synthesizing enzymes were examined. Under the assay conditions, optimized for each enzyme species, both these compounds strongly inhibited the activities of the purified human DNA polymerases alpha, beta, gamma, and DNA primase as well as those of DNA polymerase I and RNA polymerase from Escherichia coli and Rauscher leukemia virus reverse transcriptase. ATA was particularly effective in inhibiting retroviral reverse transcriptase and cellular DNA polymerase alpha. Evans blue, which is a structural analogue of suramin, exerted its inhibitory action largely by competing with the template.primer for the same binding site of the enzyme. On the other hand, ATA inhibited most, if not all, of these enzyme activities noncompetitively with respect to either the template.primers or nucleoside 5'-triphosphate substrates. The inhibition constants for ATA were, in general, smaller than those for Evans blue.
Nakane
H
H
Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Balzarini
J
J
De Clercq
E
E
Ono
K
K
D000818:Animals; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D001391:Azo Compounds / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors; D019915:DNA Primase; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D004926:Escherichia coli / Q000201:enzymology; D005070:Evans Blue / Q000494:pharmacology*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000201:enzymology; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors; D012316:RNA Nucleotidyltransferases / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors; D014407:Tumor Cells, Cultured / Q000201:enzymology
D001391:Azo Compounds; D003509:Cyclohexanecarboxylic Acids; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D001312:Aurintricarboxylic Acid; D005070:Evans Blue; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases; D012321:DNA-Directed RNA Polymerases; D004256:DNA Polymerase I