Probing length effects and mechanism of cell penetrating agents mounted on a polyproline helix scaffold.
Cell penetrating peptides (CPP) displaying a type II polyproline helix backbone of different length and amphiphilic character were synthesized and their cellular uptake was compared. The longer CPP sequence, P14LRR, displayed a 7- to 12-fold higher uptake in MCF-7 cells as compared to its shorter counterpart, P11LRR, and a 35-fold higher uptake as compared to Tatp. These results demonstrate that an increased number of cationic and hydrophobic residues can strongly influence the extent of cellular internalization. Mechanistic investigations suggest internalization via a receptor independent endocytotic pathway with these agents.
Geisler
Iris
I
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA.
Chmielewski
Jean
J
D004705:Endocytosis; D057927:Hydrophobic and Hydrophilic Interactions; D015336:Molecular Probe Techniques; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D014407:Tumor Cells, Cultured
D010455:Peptides; C011083:polyproline