Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides

Item Type:	Article
Title:	Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides
Creators Name:	Lättig-Tünnemann, G. and Prinz, M. and Hoffmann, D. and Behlke, J. and Palm-Apergi, C. and Morano, I. and Herce, H.D. and Cardoso, M.C.
Abstract:	In addition to endocytosis-mediated cellular uptake, hydrophilic cell-penetrating peptides are able to traverse biological membranes in a non-endocytic mode termed transduction, resulting in immediate bioavailability. Here we analysed structural requirements for the non-endocytic uptake mode of arginine-rich cell-penetrating peptides, by a combination of live-cell microscopy, molecular dynamics simulations and analytical ultracentrifugation. We demonstrate that the transduction efficiency of arginine-rich peptides increases with higher peptide structural rigidity. Consequently, cyclic arginine-rich cell-penetrating peptides showed enhanced cellular uptake kinetics relative to their linear and more flexible counterpart. We propose that guanidinium groups are forced into maximally distant positions by cyclization. This orientation increases membrane contacts leading to enhanced cell penetration.
Keywords:	Arginine, Biological Transport, Cell Line, Cell Membrane, Cell-Penetrating Peptides, Cells, Guanidine, Kinetics, Molecular Structure, Animals, Mice
Source:	Nature Communications
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	2
Page Range:	453
Date:	30 August 2011
Official Publication:	https://doi.org/10.1038/ncomms1459
PubMed:	View item in PubMed

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