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

Abstract

With the aim to develop effective and low toxicity DNA condensation agents, a series of oligopeptide derived macrocyclic polyamine [12]aneN3 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 150–250μM, 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]aneN3 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.