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• W2144568772 abstract "Cell-penetrating peptides such as antennapedia, TAT, transportan and polyarginine have been extensively employed for in vitro and in vivo delivery of biologically active peptides. However, little is known of the relative efficacy, toxicity and uptake mechanism of individual protein transduction domain-peptide conjugates, factors that will be critical in determining the most effective sequence. In the present study, we show by FACS analysis that unconjugated antennapedia, TAT, transportan and polyarginine demonstrate similar kinetic uptake profiles, being maximal at 1-3 h and independent of cell type (HeLa, A549 and CHO cell lines). A comparison of the magnitude of uptake of cell-penetrating peptide conjugates demonstrated that polyarginine=transportan>antennapedia>TAT. However, examination of cellular toxicity showed that antennapedia<TAT<transportan< intersectionpolyarginine, with antennapedia-peptide conjugates having no significant toxicity even at 100 microM. Confocal studies of the mechanism of antennapedia- and TAT-peptide uptake showed that the time course of uptake and their cellular distribution did not correlate with transferrin, a marker of clathrin-mediated endocytosis. In contrast, the peptides co-localised with a marker of lipid rafts domains, cholera toxin, which was attenuated following the disruption of these domains using methyl-beta-cyclodextrin. Overall, comparison of the uptake and toxicity suggests that antennapedia provides the optimal cell-penetrating peptide for peptide delivery in vitro and that both antennapedia- and TAT-mediated peptide delivery occurs predominantly via lipid raft-dependent but clathrin-independent endocytosis." @default.
• W2144568772 created "2016-06-24" @default.
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• W2144568772 date "2005-08-01" @default.
• W2144568772 modified "2023-10-14" @default.
• W2144568772 title "Characterisation of cell-penetrating peptide-mediated peptide delivery" @default.
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• W2144568772 doi "https://doi.org/10.1038/sj.bjp.0706279" @default.
• W2144568772 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1576229" @default.
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• W2144568772 hasPublicationYear "2005" @default.
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