Anthramycin is known to react firmly with DNA, but no chemical basis for this interaction has been elucidated. Since anthramycin readily undergoes hydrolytic changes at C-11, the possible relation of this reaction to the interaction with DNA was considered. Both the hydrolysis of an 11-methoxy group and the reaction with DNA were found to be H+catalysed, thus supporting a relation between the two processes. The titration of H+from the phenolic group at Position 9 of anthramycin was found to be absent in the DNA complex, suggesting that Position 9 also is involved in the complex. The rate of reaction of anthramycin-11-methyl ether with DNA was found to be increased by prior hydrolysis. The rate of reaction with DNA, however, does not involve a rate-limiting conversion of anthramycin to a reactive component, since the kinetics of the reaction were found to be basically bimolecular. This excluded the possibility that a slow conformational change of the DNA was rate-limiting. The findings support the proposal that the binding of anthramycin to DNA is covalent, and that Positions 11 and 9 are involved in the binding. The bimolecular rate constant was found to decrease exponentially with the extent of DNA reaction, probably due to neighboring-site exclusion effects. The site of reaction involves guanine, since only guanine-containing deoxypolynucleotides were found to be reactive, and since reaction of DNA with anthramycin caused stochiometric elimination of binding sites of actinomycin. © 1974.
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