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

摘要: A variety of spectroscopic and biochemical techniques have been employed to investigate the extent which binding DNA an intercalator (amsacrine or its 4-carboxamide derivative SN16713) affects netropsin, a minor groove-targeted ligand, vice versa. In general, rather little mutual interference has found one drug is compatible with other. The anilinoacridines exert no effect on positioning netropsin in groove, judged by circular dichroism spectroscopy electric linear dichroism, whereas perceptible intercalative amsacrine, but not that SN16713. Neither acridine prevents netropsin-induced Z-->B structure reversion observed poly(dG-dC).poly(dG-dC) buffer containing 60% ethanol. kinetics dissociation any from complex are affected little, if at all, simultaneous presence Footprinting experiments several drugs singly combination reveal certain amount interference, selective recognition AT-rich sequences tends dominate pattern largely maintained considerable excess amsacrine derivative.