Due to their enhanced stability and cell permeablity, cyclic cell penetrating peptides have been widely used as delivery vectors
for transporting cell-impermeable cargos into cells. In this study, we synthesized a panel of conformationally constrained
peptides with either α-helix or β-hairpin conformations. We tuned amphiphilicity of these constrained peptides with different
distribution of charged or hydrophobic residues and compared their cellular uptake efficiencies in different cell lines. We
found that the amphipathicity of these conformationally constrained peptides correlates well with their cellular uptake
efficiency. We proposed that peptides with larger hydrophobic moment (HM) have stronger binding affinity with the cell
membrane which further accelerates the endocytosis process. This finding should provide an approach towards the design of
more potent conformationally constrained cell penetrating peptides for biomedical applications
Link: http://pubs.rsc.org/en/content/articlepdf/2017/sc/c7sc03614k