We present a comparative study of calorimetrically derived thermodynamic proffles for the binding of a series of drugs with selected DNA
poly[d(A-T)]-poly[d(A-T)] behaves thermody-namically as the more "normal" host duplex toward drug binding, whereas the entropy-driven binding to the poly(dA)-poly(dT) duplex represents "aberrant" behavior. Furthermore, since each of the four drugs exhibits different modes of DNA binding, we conclude that the observed entropy-driven behavior for binding to poly(dA)-poly(dT) reflects an intrinsic property of the homopolymer duplex that is perturbed in a common manner upon ligation rather than a common property of all four binding ligands. To rationalize the large positive entropy changes that drive drug complexation with the poly-(dA)-poly(dT) duplex, we propose a model that emphasizes binding-induced perturbations of the more highly hydrated, altered B conformation of the homopolymer. Our results suggest that an aberrant thermodynamic binding proffle may reflect an unusual DNA conformation in the host duplex. However, before such a conclusion can be reached, complete