Secondary structures and cell-penetrating abilities of arginine-rich peptide foldamers.

Foldamers, which are folded oligomers with well-defined conformations, have been recently reported to have a good cell-penetrating ability. α,α-Disubstituted α-amino acids are one such promising tool for the design of peptide foldamers. Here, we prepared four types of L-arginine-rich nonapeptides containing L-leucine or α,α-disubstituted α-amino acids, and evaluated their secondary structures and cell-penetrating abilities in order to elucidate a correlation between them. Peptides containing α,α-disubstituted α-amino acids had similar resistance to protease digestion but showed different secondary structures. Intracellular uptake assays revealed that the helicity of peptides was important for their cell-penetrating abilities. These findings suggested that a peptide foldamer with a stable helical structure could be promising for the design of cell-penetrating peptides.