Equilibrium studies on the interaction of daunomycin with deoxypolynucleotides

Fluorescence and absorbance methods were used to study the interaction of daunomycin with four deoxypolynucleotides. The binding may be described by the neighbor-exclusion model for binding ratios greater than 0.05, with intrinsic binding constants decreasing in the order poly[d(A-T)] X poly[d(A-T)] greater than poly[d(G-C)] X poly[d(G-C)] greater than poly(dG) X poly(dC) greater than poly(dA) X poly(dT). The exclusion parameter was found to be approximately 2 for the A-T-containing polynucleotides, 4 for the alternating G-C polymer, and nearly 10 for poly(dG) X poly(dC). Poly(dA) X poly(dT) showed positive cooperativity at low binding ratios. Thermal denaturation studies provided quantitative support for the measured binding parameters; the delta Tm values measured may be correlated primarily with the differences seen in the exclusion parameter. Sedimentation velocity experiments on daunomycin-deoxypolynucleotide complexes show an unusual nonlinear dependence of Sapp on the binding ratio for poly[d(A-T)] X poly[d(A-T)], poly[d(G-C)] X poly[d(G-C)], and poly(dA) X poly(dT), indicative of either a nonstandard conformational change accompanying intercalation or cooperative drug binding.