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


We examined the effect of adriamycin on kinetics of DNA synthesis ...
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.



Mutational Analysis, Enzyme Substrate Interactions

One line summary:

Adriamycin and Daunorubicin binding to DNA have varying effects on the rate of DNA replication by the T4 DNA polymerase


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