Plasmid DNA delivery using arginine-rich cell-penetrating L/D-peptides containing α-aminoisobutyric acids

The relationship between intracellular uptake efficacy and the folding behavior of arginine-rich cell-penetrating L/D-peptides with α,α-disubstituted α-amino acids in plasmid DNA (pDNA) delivery was examined. Nano-sized complexes formed from pDNA and L/D-peptides efficiently traversed the cell membrane regardless of the peptide conformation. This finding represents a significant deviation from previously reported covalent cargo delivery methods using cell penetrating peptides with L- and D-amino acids.