Inhibition of DNA Polymerases α and γ by Rifamycin Derivative AF/0131

Publisher Website
Google Scholar
Abstract
The nature of the inhibitory effects of rifamycin derivative AF/013 (O-n-octyloxime of rifamycin SV) on DNA polyinerases α and γ were studied. Lineweaver-Burk analysis of the inhibition of DNA polymerases with respect to a substrate and template-primer showed a different mode of inhibition by AF/013 for each: the inhibition of DNA polymerase γ was competitive with both dTTP and poly(rA) oligo(dT), while that of DNA polymera.se α was competitive with activated calf thymus DNA and non-competitive with dTTP. Further analysis of the competitive mode of the inhibition of DNA polymerase α, using poly(dT)-oligo(rA) as a template-primer, demonstrated that the primer molecule competed with AF/013. A change of effective divalent metal ion (Mn2+ in place of Mg2+) in the reaction mixture did not alter this competitive mode of inhibition with respect to the templateprimer. The results of experiments to obtain further insight into the mechanism of drug-enzyme interaction suggest that AF/013 binds tightly to DNA polymerase α, and inhibits the process of chain elongation with DNA polymerases α and γ.

This publication has 11 references indexed in Scilit: