Anthracycline antibiotics. Interaction with DNA and nucleosomes and inhibition of DNA synthesis.
We report studies of the interaction of four anthracycline antibiotics, iremycin (IM), daunomycin (DM), aclacinomycin A (AM), and violamycin B1 (VM), with naked DNA, nucleosomal core particles, and 175 base pair (bp) nucleosomes lacking histone H1. In all cases the binding strength increases in the order IM less than DM approximately AM less than VM. The binding substrates increased in affinity for the drugs in the following order: core particles less than 175-bp nucleosomes less than DNA. The apparent DNA length increment per drug bound decreases in the progression IM greater than DM greater than AM greater than VM, the same serial order as is characterized by increasing binding affinity. Dichroism amplitude measurements show that for all drugs the long-wavelength absorbance transition moment is tilted by 26-29 degrees relative to the plane perpendicular to the helix axis; this angle probably corresponds to the long axis tilt of the intercalated chromophore. Finally, it was found that the ability of the drugs to inhibit DNA synthesis by Escherichia coli DNA polymerase I increases in the same order as their binding affinity.
Fritzsche
H
H
Wähnert
U
U
Chaires
J B
JB
Dattagupta
N
N
Schlessinger
F B
FB
Crothers
D M
DM
D015250:Aclarubicin; D000617:Aminoglycosides / Q000494:pharmacology; D018943:Anthracyclines; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D004256:DNA Polymerase I / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects*; D003630:Daunorubicin / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D009279:Naphthacenes / Q000494:pharmacology; D009707:Nucleosomes / Q000187:drug effects*
D000617:Aminoglycosides; D018943:Anthracyclines; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D009707:Nucleosomes; C010806:violamycins; D015250:Aclarubicin; C028700:iremycin; D004247:DNA; D004256:DNA Polymerase I; D003630:Daunorubicin