Tuning the DNA Conformational Perturbations Induced by Cytotoxic Platinum−Acridine Bisintercalators: Effect of Metal Cis/Trans Isomerism and DNA Threading Groups

Abstract

Four highly charged, water soluble platinum−acridine bisintercalating agents have been synthesized. Depending on the cis/trans isomerism of the metal and the nature of the acridine side chains, bisintercalation induces/stabilizes the classical Watson−Crick B-form or a non-B-form. Circular dichroism spectra and chemical footprinting experiments suggest that 4, the most active derivative in HL-60 cells, produces a structurally severely perturbed DNA with features of a Hoogsteen base-paired biopolymer