Pillar[5]arene–modified peptide-guanidiniocarbonylpyrrol amphiphiles with gene transfection properties

Pillar[5]arene–modified amphiphilic peptides with varying numbers of guanidiniocarbonylpyrrol (GCP) moieties have been successfully synthesized, which can self-assemble to multivalent cationic superstructures in aqueous solutions. These assembled peptides can condense DNA into various compact multimolecular aggregates to achieve successful intracellular DNA delivery and demonstrate great potential for gene transfection. Transfection efficiencies of the self-assembled superstructures have been evaluated in vitrowith HeLa and HEK 293T cells. We demonstrate that GCP moiety could enhance the cell transfection ability, owing to its excellent binding towards cytomembrane. It was also found that subtle structure difference in peptides 2and 3could result in distinct transfection efficacy, which makes it possible to gain an in-depth understanding of their structure-activity relationship. This work presents a good example of rational structural design in achieving effective gene transfection vectors.