Differential inhibition of various mammalian DNA polymerase activities by ammonium 21‐tungsto‐9‐antimoniate (HPA23)

Abstract

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 α and murine DNA polymerase γ. HPA23 inhibited the activity of DNA polymerase α in noncompetitive fashion with respect to either deoxynucleotide substrate or nucleic acid template · primer. The Ki of murine DNA polymerase α for HPA23 was determined to be 24 nM. The activity of mouse DNA polymerase γ 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 β 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. Copyright © 1988, Wiley Blackwell. All rights reserved