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).

Relating structure and internalization for ROMP-based protein mimics

“…38 As demonstrated here and by others, the hydrophobic domain of the PTDM is important to protein internalization. 38,39 The block copolymer outperformed all other polymers tested at protein delivery yielding an MFI around 20 times higher, as determined by FCM (Figure 5B). This was corroborated with confocal images, which revealed both punctate and diffuse fluorescence within the imaged cells (Figure 5A).…”

Intracellular delivery of quantum dots mediated by a histidine- and arginine-rich HR9 cell-penetrating peptide through the direct membrane translocation mechanism

“…By the same token, both Pas-modification and N-terminal acylation of arginine-rich CPPs (PasR8 and C6R8) were developed to significantly improve delivery efficiency by raising hydrophobicity [43,46]. Studies have shown that the guanidinium-head groups of arginines were crucial for cellular uptake due to their interactions with membrane phospholipids, as substituting nitrogen of guanidine with oxygen reduced the ability of transduction [60,63].…”

“…Lo and Wang discovered that a PTD of TAT comprised of additional polyhistidine and cysteine residues possessed endosomolytic properties and increased the gene expression of DNAs carried by this CPP [42]. Takayama et al reported that a short Pas (FFLIPKG) peptide enhanced the intracellular delivery of octaarginine within 5 min, even in the presence of serum [43].…”

Promises of Apoptosis-Inducing Peptides in Cancer Therapeutics

“…CPPs can be used in vivo to deliver their cargo to virtually all tissues [43]. Methodologies based on CPPs are constantly being improved as demonstrated by the recent characterization of penetration accelerating sequences (PAS) that significantly increase the cytosolic release of CPPs taken up by cells [44].…”