Syntheses of [12]aneN₃-oligopeptide conjugates as effective DNA condensation agents

With the aim to develop effective and low toxicity DNA condensation agents, a series of oligopeptide derived macrocyclic polyamine [12]aneN(3) conjugates 7a-h·3HCl have been designed and synthesized through multi-step amidation reactions. Structure-property study through gel electrophoresis proved that the conjugates containing high hydrophobic ending amino acids exhibited effective condensation ability at concentration of 150-250 μM, which was further confirmed by dynamic light scattering and atomic force microscopy experiments. EB displacement assay, ionic salt effect, and structure-property relationship in gel electrophoresis indicated that DNA condensation resulted from both the electrostatic interaction of [12]aneN(3) unit and hydrogen-bonding/hydrophobic multi-interaction of oligopeptide moiety in the conjugates with DNA. The reversible condensation process and their low cytotoxicity suggest that the new condensing agents are potential for the development of non-viral vectors.