Mechanism of the Inhibition of Calf Thymus DNA Polymerases α and β by Daunomycin and Adriamycin
1980 年 87 巻 3 号 p. 911-918
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1980 年 87 巻 3 号 p. 911-918
The anthracycline antibiotics, daunomycin and adriamycin, strongly inhibited the reactions of both DNA polymerase α and β from calf thymus by competing with the template primers, i.e., activated DNA or initiated deoxyhomopolymers. DNA polymerase α was more sensitive to both drugs than DNA polymerase β with all the template-primers tested. With poly (dT)• oligo (dA), the activity of the α-enzyme was extremely sensitive to these drugs (K1, 0.9μm for daunomycin), while that of the β-enzyme was relatively resistant (K1, 25μm for dauno-mycin).
Much stronger inhibition was produced by preincubating these drugs with the enzymes than with the template-primers, and the inhibition of DNA polymerase activity was reversed by the addition of excess template-primers. These results indicate that the inhibition was produced mainly by direct interaction of the drugs with DNA polymerases rather than by impairing the template activity of DNA due to intercalation of the drugs.
Although adriamycin inhibited DNA polymerases α and β to slightly higher extents than daunomycin, the modes of inhibition by these two drugs were quite similar.
