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.
D003090:Coliphages / Q000201:enzymology*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D013329:Structure-Activity Relationship; D013698:Templates, Genetic
D004317:Doxorubicin; D004259:DNA-Directed DNA Polymerase