Molecular Pharmacology, Vol 11, 716-721, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Equilibrium and Kinetic Measurements of Actinomycin Binding to Deoxyribonucleic Acid in the Presence of Competing Drugs

¹ Department of Chemistry, Queens College of the City University of New York, Flushing, New York 11367

Competitive binding studies were performed by addition of daunomycin, ethidium bromide, and mithramycin to DNA-bound actinomycin D. Equilibrium and kinetic measurements demonstrated that these drugs displace actinomycin from its strong binding sites on DNA. Actinomine, an analogue of actinomycin that lacks the peptide lactones, did not displace DNA-bound actinomycin under conditions similar to those used for daunomycin, mithramycin, ethidium bromide, and an ethidium analogue in which the phenyl group is replaced by a methyl group. The competing drugs may modify actinomycin-DNA interaction by interfering with binding of the cyclic peptides of actinomycin and by inducing a structural distortion in DNA.