Biophysical Properties of Membrane-Active Peptides Based on Micelle Modeling: A Case Study of Cell-Penetrating and Antimicrobial Peptides

2010 ◽  
Vol 114 (43) ◽  
pp. 13726-13735 ◽  
Author(s):  
Qian Wang ◽  
Gongyi Hong ◽  
Glenn R. Johnson ◽  
Ruth Pachter ◽  
Margaret S. Cheung
Keyword(s):  
Antimicrobial Peptides ◽  
Biophysical Properties ◽  
Active Peptides ◽  
Cell Penetrating ◽  
Membrane Active Peptides

scholarly journals Membrane Active Peptides and Their Biophysical Characterization

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 77 ◽  
Author(s):  
Fatma Gizem Avci ◽  
Berna Sariyar Akbulut ◽  
Elif Ozkirimli
Keyword(s):  
Antimicrobial Peptides ◽  
Single Molecule ◽  
Imaging Techniques ◽  
Membrane Integrity ◽  
Cell Penetrating Peptides ◽  
Single Molecule Level ◽  
Active Peptides ◽  
Cell Penetrating ◽  
Biophysical Techniques ◽  
Membrane Active Peptides

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.

How charge distribution influences the function of membrane-active peptides: Lytic or cell-penetrating?

2017 ◽  
Vol 83 ◽  
pp. 71-75 ◽  
Author(s):  
Long Chen ◽  
Qiang Zhang ◽  
Xiushuang Yuan ◽  
Yimeng Cao ◽  
Yanyan Yuan ◽  
...  
Keyword(s):  
Charge Distribution ◽  
Active Peptides ◽  
Cell Penetrating ◽  
Membrane Active Peptides

scholarly journals Ionpair-π interactions favor cell penetration of arginine/tryptophan-rich cell-penetrating peptides

2019 ◽  
Author(s):  
Astrid Walrant ◽  
Antonio Bauzá ◽  
Claudia Girardet ◽  
Isabel D. Alves ◽  
Sophie Lecomte ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Density Functional ◽  
Molecular Mechanisms ◽  
Cell Penetrating Peptides ◽  
Membrane Phospholipids ◽  
Active Peptides ◽  
Π Interactions ◽  
Cell Penetrating ◽  
Membrane Active Peptides

AbstractCell-penetrating peptides (CPPs) internalization can occur both by endocytosis and direct translocation through the cell membrane. These different entry routes suggest that molecular partners at the plasma membrane, phospholipids or glycosaminoglycans (GAGs), bind CPPs with different affinity or selectivity. The analysis of sequence-dependent interactions of CPPs with lipids and GAGs should lead to a better understanding of the molecular mechanisms underlying their internalization. CPPs are short sequences generally containing a high number of basic arginines and lysines and sometimes aromatic residues, in particular tryptophans. Tryptophans are crucial residues in membrane-active peptides, because they are important for membrane interaction. Membrane-active peptides often present facial amphiphilicity, which also promote the interaction with lipid bilayers. To study the role of Trp and facial amphiphilicity in cell interaction and penetration of CPPs, a nonapeptide series containing only Arg, Trp or D-Trp residues at different positions was designed. Our quantitative study indicates that to maintain/increase the uptake efficiency, Arg can be advantageously replaced by Trp in the nonapeptides. The presence of Trp in oligoarginines increases the uptake in cells expressing GAGs at their surface, when it only compensates for the loss of Arg and maintains similar peptide uptake in GAG-deficient cells. In addition, we show that facial amphiphilicity is not required for efficient uptake of these nonapeptides. Thermodynamic analyses point towards a key role of Trp that highly contributes to the binding enthalpy of complexes formation. Density functional theory (DFT) analysis highlights that salt bridge-π interactions play a crucial role for the GAG-dependent entry mechanisms.

scholarly journals EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide

2020 ◽  
Vol 477 (1) ◽  
pp. 45-60 ◽  
Author(s):  
N.G. Eissa ◽  
E.J. Sayers ◽  
D. Birch ◽  
S.G. Patel ◽  
Y.-H. Tsai ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Cell Penetrating Peptides ◽  
Cell Physiology ◽  
Cellular Delivery ◽  
Membrane Interactions ◽  
Active Peptides ◽  
Juxtamembrane Region ◽  
Protein Membrane ◽  
Cell Penetrating ◽  
Membrane Active Peptides

Membrane-active peptides have been extensively studied to probe protein–membrane interactions, to act as antimicrobial agents and cell-penetrating peptides (CPPs) for the delivery of therapeutic agents to cells. Hundreds of membrane-active sequences acting as CPPs have now been described including bioportides that serve as single entity modifiers of cell physiology at the intracellular level. Translation of promising CPPs in pre-clinical studies have, however, been disappointing as only few identified delivery systems have progressed to clinical trials. To search for novel membrane-active peptides a sequence from the EGFR juxtamembrane region was identified (named EJP18), synthesised, and examined in its L- and D-form for its ability to mediate the delivery of a small fluorophore and whole proteins to cancer cell lines. Initial studies identified the peptide as being highly membrane-active causing extensive and rapid plasma membrane reorganisation, blebbing, and toxicity. At lower, non-toxic concentrations the peptides outperformed the well-characterised CPP octaarginine in cellular delivery capacity for a fluorophore or proteins that were associated with the peptide covalently or via ionic interactions. EJP18 thus represents a novel membrane-active peptide that may be used as a naturally derived model for biophysical protein–membrane interactions or for delivery of cargo into cells for therapeutic or diagnostic applications.

scholarly journals Slow andad hoc: Unravelling the two features characterizing the development of bacterial resistance to membrane active peptides

2019 ◽  
Author(s):  
Ayan Majumder ◽  
Meher K. Prakash
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Serial Passage ◽  
Membrane Composition ◽  
Drug Pressure ◽  
Active Peptides ◽  
Development Of Resistance ◽  
Membrane Adaptation ◽  
Membrane Active Peptides ◽  
Drug Free

AbstractMembrane disrupting drugs such as antimicrobial peptides are being considered as a solution to counter the problem of antibiotic resistance. Although it can be intuitively imagined that bacteria will eventually develop resistance to this class of drugs as well, the concern has largely been ignored. Drawing upon the experimental data from the resistance ofStaphylococcus aureusto antimicrobial peptides, we theoretically model the membrane adaptation under drug pressure. Using our model, we simulate the serial passage experiments with and without the drug pressure, and use the comparisons with experiments to estimate the unknown kinetic parameters. While the development of resistance to enzyme or membrane targeting drugs are both driven by spontaneous mutations, an additional lysylation step required in the latter slows the development of resistance. By quantifying the tradeoff between the gain in fitness under drug pressure and a loss in growth due to membrane modification, our model shows a fast reversal of membrane composition in drug free conditions, re-sensitizing the bacterium to the drugs.

Biophysics meets membrane-active peptides

2008 ◽  
Vol 14 (4) ◽  
pp. 365-367
Author(s):  
Miguel A. R. B. Castanho ◽  
Margitta Dathe
Keyword(s):  
Active Peptides ◽  
Membrane Active Peptides
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