Enhanced intracellular delivery using arginine-rich peptides by the addition of penetration accelerating sequences (Pas)

Cell penetrating peptides (CPPs), including arginine-rich peptides, are attractive tools for the intracellular delivery of various bioactive molecules with a low membrane permeability. We showed that the accelerated intracellular delivery of arginine-rich peptides was achieved by the addition of a short peptide segment (penetration accelerating sequence, Pas) to arginine-rich CPPs. The cytosolic release of the Pas-attached arginine-rich CPPs was observed within 5 min after the treatment of the cells with the peptides even in the presence of serum. Effectiveness of the Pas segment in the intracellular delivery of bioactive peptides using arginine-rich CPPs was exemplified through the enhanced growth inhibition activity of the malignant glioma cells by a retro-inverso peptide derived from the p53 C-terminal 22-amino-acid segment (positions 361–382).

Graphical abstractAddition of a small peptide segment called a penetration accelerating sequence (Pas) significantly enhances the internalization efficiency of arginine-rich cell penetrating peptides (CPPs).Figure optionsDownload full-size imageDownload as PowerPoint slide