Differential inhibition of various mammalian DNA polymerase activities by ammonium 21-tungsto-9-antimoniate (HPA23).
The 21-tungsto-9-antimoniate ammonium salt (HPA23), known as an antiviral agent, has been shown to be a potent inhibitor of both human and murine DNA polymerase alpha and murine DNA polymerase gamma. HPA23 inhibited the activity of DNA polymerase alpha in noncompetitive fashion with respect to either deoxynucleotide substrate or nucleic acid template.primer. The Ki of murine DNA polymerase alpha for HPA23 was determined to be 24 nM. The activity of mouse DNA polymerase gamma also was strongly inhibited by HPA23 (Ki, 20 nM), and the mode of inhibition was competitive with respect to the template.primer, (rA)n.(dT)12-18, and noncompetitive to substrate, dTTP. DNA polymerase beta and terminal deoxynucleotidyltransferase, however, were relatively resistant to inhibition by HPA23. The observed inhibitions by HPA23 seem to be closely related to the polyanionic property of this drug.
Ono
K
K
Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Nakane
H
H
Barré-Sinoussi
F
F
Chermann
J C
JC
D000818:Animals; D000965:Antimony / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors; D006678:HIV / Q000201:enzymology; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D014414:Tungsten / Q000494:pharmacology*; D017973:Tungsten Compounds
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D017973:Tungsten Compounds; C009613:ammonium tungsten antimonate hydroxide oxide; D000965:Antimony; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D014414:Tungsten