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Molecular Pharmacology, Vol 16, 357-360, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Dissociation of Polydeoxynucleotide-Daunomycin Complexes

M. GRANT 1 and D. R. PHILLIPS 1

1 Inorganic Chemistry Department and Biochemistry Department, La Trobe University, Bundoora, Victoria 3083, Australia

The first order rate constants for the dissociation of daunomycin from polydeoxynucleotides have been measured at 20° and 37°. The rate constants at a given temperature were similar and were in the order poly(dA)·poly(dT) > poly(dG)·poly(dC) > poly(dA-dT)· poly(dA-dT) > poly(dG-dC)·poly(dG-dC) at both temperatures. A comparison of these data with inhibition studies of DNA polymerase (using the same polydeoxynucleotide templates) indicates that at the DNA level, the mechanism of action of daunomycin is primarily due to disruption of the DNA secondary structure (i.e., dependent on the amount of daunomycin bound to the DNA template) but is not directly dependent on the rate of release of daunomycin from the DNA.

Note:
ACKNOWLEDGMENTS The technical assistance of Miss Gayle Carlyle is acknowledged, as is the gift of daunomycin from Farmitalia, Milan.

Submitted on January 23, 1978
Accepted on November 28, 1978






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