Adriamycin interactions with T4 DNA polymerase. Two modes of template-mediated inhibition.

We examined the effect of adriamycin on kinetics of DNA synthesis catalyzed by DNA polymerase purified from bacteriophage T4-infected Escherichia coli. Two distinct modes of enzyme inhibition occur: uncompetitive and competitive at "low" and "high" drug:DNA nucleotide molar ratios, respectively. Competitive inhibition is not observed unless an unblocked amino group is present on the sugar (daunosamine) moiety. A model is proposed to relate the enzyme inhibition kinetics to intercalative and ionic binding of adriamycin to DNA.