CELLULAR UPTAKE OF S4(13)-PV CELL PENETRATING PEPTIDE: AN ENDOCYTOSIS- INDEPENDENT PROCESS FOLLOWING PEPTIDE CONFORMATIONAL CHANGES INDUCED BY PEPTIDE-MEMBRANE INTERACTIONS

摘要

Cell penetrating peptides have been successfully used to mediate the intracellular delivery of a wide variety of molecules in vitro and in vivo, although the mechanisms by which cellular uptake occurs remain a matter of extensive debate, Recently, we conducted a systematic analysis of the mechanism underlying the cellular uptake of the S4(13)-PV cell penetrating peptide, a chimeric peptide that results from the combination of a 13 amino acid sequence, derived from the Dermaseptin S4 peptide, with the nuclear localization signal of the SV40 large-T antigen (Table 1). We reported that the S4(13)-PV peptide accumulates inside cells very efficiently through a rapid, dose-dependent and non-toxic process. Studies addressing the effect of several drugs, as well as experiments involving overexpression of a dominant-negative mutant of dynamin, consistently excluded endocytosis as the mechanism responsible for the cellular uptake of this peptide.