Synthetic DNA Ligands Conjugated with Metal Binding Moiety. Regulation of the Interaction with DNA by Metal Ions and the Ligand Effect on Metal Assisted DNA Cleaving

Abstract

Abstract Various functionalized molecules were synthesized by covalently conjugating DNA intercalators with metal chelators which carry such metal-binding functional groups as ethers, polyamines, and carboxylates. Systematic studies were made on the interaction of these conjugates with DNA in the presence and in the absence of metal ions. DNA binding of the conjugates were strongly affected by coexisting metal ions. This can be accounted for by the change in the net charge and in the conformation of the conjugates through complexation with metal ions. In some of the complexes thus obtained (DNA-intercalator-metal ion ternary complexes), DNA underwent a metal assisted cleavage of the strand, the activities of which were highly dependent on the nature of metal chelating moieties adopted. It is likely that a residual Lewis acidity on the metal in the complex and the strain in the DNA backbone induced by intercalation contribute to facilitate DNA cleavage.