Protein Cargo Delivery Properties of Cell-Penetrating Peptides. A Comparative Study

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• 作者：Pille S&auml ; &auml ; lik ; Anna Elmquist ; Mats Hansen ; K&auml ; rt Padari ; Kü ; lliki Saar ; Kaido Viht ; Ü ; lo Langel ; and Margus Pooga
• 刊名：Bioconjugate Chemistry
• 出版年：2004
• 出版时间：November 2004
• 年：2004
• 卷：15
• 期：6
• 页码：1246 - 1253
• 全文大小：307K
• 年卷期：v.15,no.6(November 2004)
• ISSN：1520-4812

文摘

Application of cell-penetrating peptides for delivering various hydrophilic macromolecules withbiological function into cells has gained much attention in recent years. We compared the proteintransduction efficiency of four cell-penetrating peptides: penetratin, Tat peptide, transportan, andpVEC and studied the effects of various medium parameters on the uptake. Depletion of cellularenergy and lowering of temperature strongly impaired the internalization of protein complexed withcell-penetrating peptides, confirming the endocytotic mechanism of peptide-mediated protein cellulartransduction. Peptide-induced protein association with HeLa cells decreased 3-6-fold in energy-depleted cells. Inhibition of clathrin-dependent endocytosis by the hyperosmolar medium decreasedthe uptake of peptide-avidin complexes 1.5-3-fold and the removal of cholesterol from the plasmamembrane 1.2-2-fold, suggesting that both clathrin-dependent and independent endocytosis wereinvolved in peptide-induced cellular delivery of avidin. However, even under conditions of cellularenergy depletion, ceasing of cellular traffic, and partial depolarization of plasma membrane, peptide-protein complexes associated with HeLa cells, as observed by FACS analysis and spectrofluorimetry.Among the studied peptides, pTat and transportan revealed higher protein transduction efficiencythan penetratin or pVEC.