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The reaction of doxorubicin and dna at high nucleotide to drug ratios

, : The reaction of doxorubicin and dna at high nucleotide to drug ratios. European Journal of Medicinal Chemistry 15(5): 469-472

The interactions of the monocation of the antitumor, anthracycline antibiotic doxorubicin with calf thymus DNA were studied. In the intercalative region, with high DNA phosphate to cation ratios, the drug is sequestered by 4 phosphate groups. A nonlinear isotherm based on the assumption that the monocation is bound by 2 sites, each containing 2 DNA-phosphate units, yields a satisfactory equilibrium expression. The region in which the intercalative sites are saturated and surface binding predominates can be adequately described by a linear isotherm. Computerized curve-fitting of the data generated binding constants of 1.3 .times. 10912M-2 for the intercalative region and 1.6 .times. 105 1 M-1 for the surface binding at a pH < 2 U below the pKa [negative log of the Ka] of the monocation.


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