Temperature Dependence of the Volumetric Parameters of Drug Binding to Poly[d(A-T)]·Poly[d(A-T)] and Poly(dA)·Poly(dT)

We report the temperature and salt dependence of the volume change (ΔVb) associated with the binding of ethidium bromide and netropsin with poly(dA)·poly(dT) and poly[d(A-T)]·poly[d(A-T)]. The ΔVb of binding of ethidium with poly(dA)·poly(dT) was much more negative at temperatures ∼70°C than at 25°C, whereas the difference is much smaller in the case of binding with poly[d(A-T)]·poly[d(A-T)]. We also determined the volume change of DNA-drug interaction by comparing the volume change of melting of DNA duplex and DNA-drug complex. The DNA-drug complexes display helix-coil transition temperatures (Tm) several degrees above those of the unbound polymers, e.g., the Tm of the netropsin complex with poly(dA)poly(dT) is 106°C. The results for the binding of ethidium with poly[d(A-T)]·poly[d(A-T)] were accurately described by scaled particle theory. However, this analysis did not yield results consistent with our data for ethidium binding with poly(dA)·poly(dT). We hypothesize that heat-induced changes in conformation and hydration of this polymer are responsible for this behavior. The volumetric properties of poly(dA)·poly(dT) become similar to those of poly[d(A-T)]·poly[d(A-T)] at higher temperatures.