title: Enhanced intracellular delivery using arginine-rich peptides by the addition of penetration accelerating sequences (Pas).
abstract: 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).
authors.affiliation: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takayama
authors.forename: Ikuhiko
authors.initials: I
authors.lastname: Nakase
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Michiue
authors.forename: Toshihide
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsui
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
mesh_terms: 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
chemical_list: D036022:Capsid Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53; C500307:octa-arginine peptide; D001120:Arginine; D002402:Cathepsin D