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).
Takayama
Kentaro
K
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
Nakase
Ikuhiko
I
Michiue
Hiroyuki
H
Takeuchi
Toshihide
T
Tomizawa
Kazuhito
K
Matsui
Hideki
H
Futaki
Shiroh
S
D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D036022:Capsid Proteins / Q000737:chemistry; D002402:Cathepsin D / Q000737:chemistry*; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D036022:Capsid Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53; C500307:octa-arginine peptide; D001120:Arginine; D002402:Cathepsin D