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Journal of Chemistry
Volume 2013 (2013), Article ID 851915, 9 pages
Research Article

The Uptake Mechanism of the Cell-Penetrating pVEC Peptide

Chemical Engineering Department, Bogazici University, Bebek, 34342 Istanbul, Turkey

Received 17 December 2012; Revised 8 March 2013; Accepted 10 March 2013

Academic Editor: Yifat Miller

Copyright © 2013 Ihsan Omur Akdag and Elif Ozkirimli. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Peptide based drug design efforts have gained renewed interest with the discovery of cargo-carrying or cell-penetrating peptides. Understanding the translocation mechanism of these peptides and identifying the residues or elements that contribute to uptake can provide valuable clues toward the design of novel peptides. To this end, we have performed steered molecular dynamics (SMD) simulations on the pVEC peptide from murine vascular endothelial-cadherin protein and its two variants. Translocation was found to occur in three stages, adsorption via the cationic residues, inclusion of the whole peptide inside the membrane accompanied by formation of a water defect, and exit of both peptide and water molecules from the bilayer. Our simulation results suggest that the precise order in which the hydrophobic, cationic, and the polar regions are located in the amphipathic pVEC peptide contributes to its uptake mechanism. These results present new opportunities for the design of novel cell-penetrating and antimicrobial peptides.