2009
DOI: 10.1016/j.febslet.2009.11.046
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Arginine‐rich cell‐penetrating peptides

Abstract: a b s t r a c tArginine-rich cell-penetrating peptides are short cationic peptides capable of traversing the plasma membranes of eukaryotic cells. While successful intracellular delivery of many biologically active macromolecules has been accomplished using these peptides, their mechanisms of cell entry are still under investigation. Recent dialogue has centered on a debate over the roles that direct translocation and endocytotic pathways play in internalization of cell-penetrating peptides. In this paper, we … Show more

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Cited by 460 publications
(480 citation statements)
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References 91 publications
(165 reference statements)
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“…Compared with guanidine, the amine group of lysine has reduced H-bonding ability and thus cannot generate the positive curvature component necessary for negative Gaussian curvature. Therefore, arginine supports generation of negative Gaussian curvature, but lysine substitutions limit peptide capability because lysine favors generation of negative mean curvature only (29,44). The electrostatically driven generation of H II phases by (R/K)-Crp4 demonstrates that the lysine-rich variant strongly interacts with and binds to membranes, just like arginine-rich native Crp4.…”
Section: Discussionmentioning
confidence: 99%
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“…Compared with guanidine, the amine group of lysine has reduced H-bonding ability and thus cannot generate the positive curvature component necessary for negative Gaussian curvature. Therefore, arginine supports generation of negative Gaussian curvature, but lysine substitutions limit peptide capability because lysine favors generation of negative mean curvature only (29,44). The electrostatically driven generation of H II phases by (R/K)-Crp4 demonstrates that the lysine-rich variant strongly interacts with and binds to membranes, just like arginine-rich native Crp4.…”
Section: Discussionmentioning
confidence: 99%
“…Geometrically, the surface will curve upwards in one direction and downwards in a perpendicular direction, locally giving it the shape of a saddle. Negative Gaussian curvature generation is a potent way to disrupt membranes because it is necessary for many different membrane destabilization processes (20,29). The H II phase is composed of lipid monolayers that have a negative mean curvature.…”
Section: Resultsmentioning
confidence: 99%
“…Internalization has consequently been suggested to occur via different routes of endocytosis, potentially including macropinocytosis, clathrin-and caveolin mediated endocytosis, as well as via a mode of entry by direct membrane penetration at high peptide concentrations. 125,[133][134][135] Although direct membrane penetration was proposed as a potential route of entry for PTDs alone, uptake of arginine-rich PTDs linked to macromolecular cargoes appears to occur solely by endocytosis. 127,134,136 Since routes of entry appear to be similar for most PTDs and delivery efficiency is subject to the same limitations, the potential applications of well-characterized PTDs are worth considering, rather than searching for the "best PTD."…”
Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning
confidence: 99%
“…131 In experiments with model membranes, HIV1-TAT-PTD entered giant unilamellar vesicles (GUVs) when model membranes contained negative intrinsic curvature lipids such as lipids with phosphatidylethanolamine headgroups. 132,133 Entry into GUVs occurred above a specific concentration threshold of peptides. 133 Experiments carried out with fluorescently labeled arginine-rich PTDs applied to live cells showed a punctuate pattern at 37°C, which indicated endosomal localization of PTDs.…”
Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning
confidence: 99%
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