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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Letter Article

Structural Plasticity of EAK-16 Peptide Inducing Vesicle Membrane Leakage

Author(s): Abdul Majid *, Farah Naz and Muhammad Hassan Khaskheli

Volume 27, Issue 8, 2020

Page: [801 - 807] Pages: 7

DOI: 10.2174/0929866527666200129141116

Price: $65

Abstract

Background: Ionic complementary peptide EAK-16 has been studies for anticancer drug delivery application. This is a 16 residues, short sequence peptide has ability to trosnform into micro/nanoparticle via self-assembly. However, it is still not clear that how this can bind with cell membrane to induce membrane leakage or delivering their cargo inside cell membrane.

Objective: The main objective of this work was to understand behaviour of secondary structure conformation of peptide in solution and at lipid membrane interfaces and membrane permeability of synthetic ionic complementary peptide EAK-16. The corresponding secondary structure conformation was evaluated.

Methods: We performed biophysical investigation to probe the interaction of synthesised ionic complementary peptide (EAK-16) with dimyristoylphospholcholine (DMPC) and dimyristoylphosphoserine (DMPS) membrane interfaces. The folding behaviours of EAK-16 were studied with Circular Dichroism (CD) spectroscopy. Membrane leakage with peptide was confirmed with calcein leakage assay.

Results: Our finding of this study showed that in aqueous phase EAK-16 was predominantly folded into β-sheets. The temperature could alter the β-sheets. However, in DMPC and DMPS membrane interfaces, EAK-16 adopted helical conformation. EAK-16 has preference in perturbing anionic compared Zwitterionic lipid vesicles. This study proposed that hydrophobic grooves of EAK-16 might be a key in the association with lipid bilayers. Secondly, a charge distribution of ionic residues would also support the orientation at lipid bilayers. This peptide membrane association would facilitate the membrane destabilisation.

Conclusion: This study demonstrated the supporting evidence that EAK-16 could interact with lipid membranes and conforming to helical structure, while the helical conformation induced the lipid membrane leakage. Overall, this study provides a physical rationale that ionic complementary peptide can be a useful tool for designing and development of novel antibiotics and anticancer agents along its previous drug delivery applications.

Keywords: Ionic complementary peptide, peptide membrane interaction, membrane permeability, peptide folding, structurefunction of peptide, zwitterionic lipid vesicles.

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