The Uptake Mechanism of the Cell-Penetrating pVEC Peptide

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 desig...

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Main Authors: Ihsan Omur Akdag, Elif Ozkirimli
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Journal of Chemistry
Online Access:http://dx.doi.org/10.1155/2013/851915
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author Ihsan Omur Akdag
Elif Ozkirimli
author_facet Ihsan Omur Akdag
Elif Ozkirimli
author_sort Ihsan Omur Akdag
collection DOAJ
description 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.
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spelling doaj-art-5a39fb140c404fe28f72793a235bbc9e2025-08-20T02:05:29ZengWileyJournal of Chemistry2090-90632090-90712013-01-01201310.1155/2013/851915851915The Uptake Mechanism of the Cell-Penetrating pVEC PeptideIhsan Omur Akdag0Elif Ozkirimli1Chemical Engineering Department, Bogazici University, Bebek, 34342 Istanbul, TurkeyChemical Engineering Department, Bogazici University, Bebek, 34342 Istanbul, TurkeyPeptide 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.http://dx.doi.org/10.1155/2013/851915
spellingShingle Ihsan Omur Akdag
Elif Ozkirimli
The Uptake Mechanism of the Cell-Penetrating pVEC Peptide
Journal of Chemistry
title The Uptake Mechanism of the Cell-Penetrating pVEC Peptide
title_full The Uptake Mechanism of the Cell-Penetrating pVEC Peptide
title_fullStr The Uptake Mechanism of the Cell-Penetrating pVEC Peptide
title_full_unstemmed The Uptake Mechanism of the Cell-Penetrating pVEC Peptide
title_short The Uptake Mechanism of the Cell-Penetrating pVEC Peptide
title_sort uptake mechanism of the cell penetrating pvec peptide
url http://dx.doi.org/10.1155/2013/851915
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