Design of composite drug molecules: mutual effects on binding to DNA of an intercalator, amsacrine, and a minor groove binder, netropsin.

A variety of spectroscopic and biochemical techniques have been employed to investigate the extent to which binding to DNA of an intercalator (amsacrine or its 4-carboxamide derivative SN16713) affects the binding of netropsin, a minor groove-targeted ligand, and vice versa. In general, rather little mutual interference has been found and the binding of one drug is compatible with binding of the other. The anilinoacridines exert little or no effect on the positioning of netropsin in the minor groove, judged by circular dichroism spectroscopy and electric linear dichroism, whereas netropsin has a perceptible effect on the intercalative binding of amsacrine, but not that of SN16713.

Binding of a distamycin-ellipticine hybrid molecule to DNA and chromatin: spectroscopic, biochemical, and molecular modeling investigations.

A bifunctional molecule in which an ellipticine chromophore is attached to a distamycin residue via a diaminopropyl tether has been designed and synthesized in the expectation of creating a hybrid molecule capable of bidentate binding to DNA by both intercalation and minor-groove interactions. The strength and mode of binding to DNA of this conjugate have been studied by means of circular and linear dichroism as well as by stopped-flow kinetics and measurements of reactivity toward a chemical probe. The results converge to reveal that the ellipticine moiety of the hybrid largely dominates the binding reaction with DNA.