pVEC hydrophobic N‐terminus is critical for antibacterial activity

Alaybeyoglu, Begum; Akbulut, Berna Sarıyar; Özkırımlı, Elif

doi:10.1002/psc.3083

Cited by 17 publications

(13 citation statements)

References 86 publications

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“…This information is especially complementary to imaging experiments with single cells [ 275 ] in describing the mechanism. Molecular Dynamics (MD) simulations [ 276 ], Monte Carlo (MC) calculations [ 277 , 278 ], and umbrella sampling [ 279 , 280 , 281 ] have provided detailed biophysical characterization of the peptide–membrane system. Simulations are commonly used on peptide–lipid bilayer systems to examine the behavior of membrane active peptides as they orient at the water–bilayer interface [ 44 ] and during or upon penetration into the membrane [ 276 ].…”

Section: Computer Simulationsmentioning

confidence: 99%

“…pVEC is an 18 amino acid long CPP, derived from murine vascular endothelial cadherin (VE-cadherin) protein, which functions as the contact between adjacent cells by hemophilic dimerization. Originally reported as a CPP, it may also act as an AMP for different cells [ 279 ]. Similar to melittin, pVEC is an amphipathic peptide with the sequence LLIILRRRIRKQAHAHSK.…”

Section: Biophysical Focus On Amphipathic Membrane Active Peptidementioning

confidence: 99%

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Membrane Active Peptides and Their Biophysical Characterization

2018

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In the last 20 years, an increasing number of studies have been reported on membrane active peptides. These peptides exert their biological activity by interacting with the cell membrane, either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. Membrane active peptides are attractive alternatives to currently used pharmaceuticals and the number of antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery in the drug pipeline is increasing. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). Antimicrobial peptides are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus, and fungi. Cell penetrating peptides are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity. Biophysical techniques shed light on peptide–membrane interactions at higher resolution due to the advances in optics, image processing, and computational resources. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Live imaging techniques allow examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provide clues on the peptide–lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

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Section: Computer Simulationsmentioning

confidence: 99%

Section: Biophysical Focus On Amphipathic Membrane Active Peptidementioning

confidence: 99%

Membrane Active Peptides and Their Biophysical Characterization

2018

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“…Originally reported as a CPP, it may also act as an AMP for different cells [261]. Similar to melittin, pVEC is an amphipathic peptide with the sequence LLIILRRRIRKQAHAHSK.…”

Section: Pvecmentioning

confidence: 99%

“…This information is especially complementary to imaging experiments with single cells [257] in describing the mechanism. Molecular Dynamics (MD) simulations [258], Monte Carlo (MC) calculations [259,260], umbrella sampling [261][262][263] have provided detailed biophysical characterization of the peptide -membrane system. MD simulations are commonly used on peptide -lipid bilayer systems to examine the behavior of membrane active peptides as they orient at the water -bilayer interface [44] and during or upon penetration into the membrane [258].…”

Section: Computer Simulationsmentioning

confidence: 99%

“…Motivated by the information that the five hydrophobic N-terminal residues (LLIIL) of pVEC are critical for its transport, their importance on transport was further investigated by SEM imaging [261]. This analysis has shown that E. coli cells treated with around 50 μM pVEC had corrugated membrane surfaces with holes and membrane ruptures while incubation with much higher concentrations of (>500 μM) del5 pVEC (the five hydrophobic N-residues truncated) did not cause cell lysis or death and only membrane blebs were visible in the SEM images.…”

Section: Pvecmentioning

confidence: 99%

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Membrane Active Peptides and Their Biophysical Characterization

Avcı

Akbulut

Özkırımlı

2018

Preprint

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In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide-membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

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Cell‐Penetrating Peptides: Correlation between Peptide‐Lipid Interaction and Penetration Efficiency

Choong

Yap

2021

ChemPhysChem

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Cell‐penetrating peptides are used in the delivery of peptides and biologics, with some cell‐penetrating peptides found to be more efficient than others. The exact mechanism of how they interact with the cell membrane and penetrate it, however, remains unclear. This study attempts to investigate the difference in free energy profiles of three cell‐penetrating peptides (TAT, CPP1 and CPP9) with a model lipid bilayer (DOPC) using molecular dynamics pulling simulations with umbrella sampling. Potential mean force (PMF) and free energy barrier between the peptides and DOPC are determined using WHAM analysis and MM‐PBSA analysis, respectively. CPP9 is found to have the smallest PMF value, followed by CPP1 and TAT, consistent with the experimental data. YDEGE peptide, however, does not give the highest PMF value, although it is a non‐cell‐permeable peptide. YDEGE is also found to form water pores, alongside with TAT and CPP9, suggesting that it is difficult to distinguish true water pore formation from artefacts arising from pulling simulations. On the contrary, free energy analysis of the peptide‐DOPC complex at the lipid‐water interface with MM‐PBSA provides results consistent with experimental data with CPP9 having the least interaction with DOPC and lowest free energy barrier, followed by CPP1, TAT and YDEGE. These findings suggest that peptide‐lipid interaction at the lipid‐water interface has a direct correlation with the penetration efficiency of peptides across the lipid bilayer.

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pVEC hydrophobic N‐terminus is critical for antibacterial activity

Cited by 17 publications

References 86 publications

Membrane Active Peptides and Their Biophysical Characterization

Membrane Active Peptides and Their Biophysical Characterization

Membrane Active Peptides and Their Biophysical Characterization

Cell‐Penetrating Peptides: Correlation between Peptide‐Lipid Interaction and Penetration Efficiency

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