Amino acid and peptide hemin derivatives as new promising virucidal agents

2012 ◽  
Vol 16 (03) ◽  
pp. 297-309 ◽  
Author(s):  
Sergei A. Okorochenkov ◽  
Galina A. Zheltukhina ◽  
Vitaly A. Roginsky ◽  
Nikolai N. Nossik ◽  
Sergei L. Zheltukhin ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Membrane Permeability ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Model System ◽  
Virucidal Activity ◽  
Liposome Membrane ◽  
Simplex Virus ◽  
Membrane Components ◽  
Modes Of Interaction

We synthesized a series of hemin derivatives (HDs) substituted by residues of amino acids and peptides at either one or two propionic-acid residues, and studied the virucidal activity of the compounds obtained against herpes simplex virus. Compounds 6,7-bis-(methyl ester N0 L-seryl)-protohemin (IX) (2) and 6,7-bis-[methyl ester N0-L-arginyl)-protohemin (IX) (6) shown the highest virucidal activity. We also investigated the interaction between HDs and lipid-membrane components as a possible mechanism of virucidal action. A model system including Clark's electrode and a micellar solution of methyl linoleate was used to quantitatively assess the capability of HDs to catalyze the oxidation of polyunsaturated fatty acids as components of lipid membranes. Another model system including liposomes that consisted of dioleoylphosphatydylcholine and was loaded with the fluorescent dye carboxyfluorescein was employed to examine the effect of HDs on lipid-membrane permeability. The kinetics and efficacy of increasing liposome-membrane permeability on exposure to HDs appeared to depend on the nature of the substituents in the HDs. The findings are strongly suggestive of the presence of two different modes of interaction between an HD and the lipid membrane, i.e. oxidative and non-oxidative mechanisms possibly underlie the virucidal action of HDs.

Extreme Elongation of Vesicles Under DC Electric Fields

2008 ◽  
Author(s):  
Mohamed M. Sadik ◽  
David I. Shreiber ◽  
Jerry W. Shan ◽  
Hao Lin
Keyword(s):  
Electrical Conductivity ◽  
Electric Fields ◽  
Lipid Membranes ◽  
Deformation Behavior ◽  
Lipid Membrane ◽  
Model System ◽  
Dominant Factor ◽  
Conductivity Ratio ◽  
Pathological Changes ◽  
Dc Electric Fields

Electrodeformation refers to the deformation of cell or vesicle lipid membranes under the application of an electric field. Such a phenomenon often accompanies electroporation processes, and also can be leveraged to detect pathological changes in cells. Recent studies have suggested that the electrical conductivity difference across the lipid membrane is a dominant factor in determining the characteristics of deformation, and various regimes of deformation were observed. Using a vesicle model system, the current work is the first report of extreme elongation of vesicles of high conductivity ratio under DC electric fields. The results suggest that the osmolarity difference between the encapsulated and bathing solutions may contribute to such abnormal deformation behavior.

scholarly journals Scaling relationships for the elastic moduli and viscosity of mixed lipid membranes

2020 ◽  
Vol 117 (38) ◽  
pp. 23365-23373 ◽  
Author(s):  
Elizabeth G. Kelley ◽  
Paul D. Butler ◽  
Rana Ashkar ◽  
Robert Bradbury ◽  
Michihiro Nagao
Keyword(s):  
Lipid Membranes ◽  
Lipid Membrane ◽  
Soft Materials ◽  
Vital Role ◽  
Single Component ◽  
Membrane Properties ◽  
Cell Functions ◽  
Bending Modulus ◽  
Membrane Components ◽  
Mixed Lipid Membranes

The elastic and viscous properties of biological membranes play a vital role in controlling cell functions that require local reorganization of the membrane components as well as dramatic shape changes such as endocytosis, vesicular trafficking, and cell division. These properties are widely acknowledged to depend on the unique composition of lipids within the membrane, yet the effects of lipid mixing on the membrane biophysical properties remain poorly understood. Here, we present a comprehensive characterization of the structural, elastic, and viscous properties of fluid membranes composed of binary mixtures of lipids with different tail lengths. We show that the mixed lipid membrane properties are not simply additive quantities of the single-component analogs. Instead, the mixed membranes are more dynamic than either of their constituents, quantified as a decrease in their bending modulus, area compressibility modulus, and viscosity. While the enhanced dynamics are seemingly unexpected, we show that the measured moduli and viscosity for both the mixed and single-component bilayers all scale with the area per lipid and collapse onto respective master curves. This scaling links the increase in dynamics to mixing-induced changes in the lipid packing and membrane structure. More importantly, the results show that the membrane properties can be manipulated through lipid composition the same way bimodal blends of surfactants, liquid crystals, and polymers are used to engineer the mechanical properties of soft materials, with broad implications for understanding how lipid diversity relates to biomembrane function.

scholarly journals Electrochemical Properties of Lipid Membranes Self-Assembled from Bicelles

Membranes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 11
Author(s):  
Damian Dziubak ◽  
Kamil Strzelak ◽  
Slawomir Sek
Keyword(s):  
Electrochemical Properties ◽  
Self Assembly ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Membrane Resistance ◽  
Electrochemical Characteristics ◽  
Freeze Thaw ◽  
Lipid Films ◽  
Supported Lipid Membranes

Supported lipid membranes are widely used platforms which serve as simplified models of cell membranes. Among numerous methods used for preparation of planar lipid films, self-assembly of bicelles appears to be promising strategy. Therefore, in this paper we have examined the mechanism of formation and the electrochemical properties of lipid films deposited onto thioglucose-modified gold electrodes from bicellar mixtures. It was found that adsorption of the bicelles occurs by replacement of interfacial water and it leads to formation of a double bilayer structure on the electrode surface. The resulting lipid assembly contains numerous defects and pinholes which affect the permeability of the membrane for ions and water. Significant improvement in morphology and electrochemical characteristics is achieved upon freeze–thaw treatment of the deposited membrane. The lipid assembly is rearranged to single bilayer configuration with locally occurring patches of the second bilayer, and the number of pinholes is substantially decreased. Electrochemical characterization of the lipid membrane after freeze–thaw treatment demonstrated that its permeability for ions and water is significantly reduced, which was manifested by the relatively high value of the membrane resistance.

scholarly journals Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 192
Author(s):  
Kinga Burdach ◽  
Dagmara Tymecka ◽  
Aneta Urban ◽  
Robert Lasek ◽  
Dariusz Bartosik ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Liquid Crystalline ◽  
Lipid Membrane ◽  
Attenuated Total Reflection ◽  
Gram Positive ◽  
Insertion Depth ◽  
Force Microscopy ◽  
Acyl Chains ◽  
Hydrophobic Portion ◽  
Membrane Fluidization

The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic lipopeptides belong to the class of the compounds which may fulfill this requirement. In this paper, we describe two linear analogues of battacin with modified acyl chains to tune the balance between the hydrophilic and hydrophobic portion of lipopeptides. We demonstrate that both compounds display antimicrobial activity with the lowest values of minimum inhibitory concentrations found for Gram-positive pathogens. Therefore, their mechanism of action was evaluated on a molecular level using model lipid films mimicking the membrane of Gram-positive bacteria. The surface pressure measurements revealed that both lipopeptides show ability to bind and incorporate into the lipid monolayers, resulting in decreased ordering of lipids and membrane fluidization. Atomic force microscopy (AFM) imaging demonstrated that the exposure of the model bilayers to lipopeptides leads to a transition from the ordered gel phase to disordered liquid crystalline phase. This observation was confirmed by attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) results, which revealed that lipopeptide action causes a substantial increase in the average tilt angle of lipid acyl chains with respect to the surface normal to compensate for lipopeptide insertion into the membrane. Moreover, the peptide moieties in both molecules do not adopt any well-defined secondary structure upon binding with the lipid membrane. It was also observed that a small difference in the structure of a lipophilic chain, altering the balance between hydrophobic and hydrophilic portion of the molecules, results in different insertion depth of the active compounds.

scholarly journals Local Enhancement of Lipid Membrane Permeability Induced by Irradiated Gold Nanoparticles

ACS Nano ◽  
2017 ◽  
Vol 11 (12) ◽  
pp. 12553-12561 ◽  
Author(s):  
Andrea Torchi ◽  
Federica Simonelli ◽  
Riccardo Ferrando ◽  
Giulia Rossi
Keyword(s):  
Gold Nanoparticles ◽  
Membrane Permeability ◽  
Lipid Membrane ◽  
Local Enhancement

scholarly journals The Structural Integrity of the Model Lipid Membrane during Induced Lipid Peroxidation: The Role of Flavonols in the Inhibition of Lipid Peroxidation

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 430 ◽  
Author(s):  
Anja Sadžak ◽  
Janez Mravljak ◽  
Nadica Maltar-Strmečki ◽  
Zoran Arsov ◽  
Goran Baranović ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Lipid Bilayers ◽  
Lipid Membranes ◽  
Structural Changes ◽  
Structural Integrity ◽  
Lipid Membrane ◽  
Membrane Properties ◽  
Structural Reorganization ◽  
Unsaturated Lipids ◽  
Oxidative Attack

The structural integrity, elasticity, and fluidity of lipid membranes are critical for cellular activities such as communication between cells, exocytosis, and endocytosis. Unsaturated lipids, the main components of biological membranes, are particularly susceptible to the oxidative attack of reactive oxygen species. The peroxidation of unsaturated lipids, in our case 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), induces the structural reorganization of the membrane. We have employed a multi-technique approach to analyze typical properties of lipid bilayers, i.e., roughness, thickness, elasticity, and fluidity. We compared the alteration of the membrane properties upon initiated lipid peroxidation and examined the ability of flavonols, namely quercetin (QUE), myricetin (MCE), and myricitrin (MCI) at different molar fractions, to inhibit this change. Using Mass Spectrometry (MS) and Fourier Transform Infrared Spectroscopy (FTIR), we identified various carbonyl products and examined the extent of the reaction. From Atomic Force Microscopy (AFM), Force Spectroscopy (FS), Small Angle X-Ray Scattering (SAXS), and Electron Paramagnetic Resonance (EPR) experiments, we concluded that the membranes with inserted flavonols exhibit resistance against the structural changes induced by the oxidative attack, which is a finding with multiple biological implications. Our approach reveals the interplay between the flavonol molecular structure and the crucial membrane properties under oxidative attack and provides insight into the pathophysiology of cellular oxidative injury.

scholarly journals The interplay between lipids and dopamine on α-synuclein oligomerization and membrane binding

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Chi L. L. Pham ◽  
Roberto Cappai
Keyword(s):  
Lipid Membranes ◽  
Amyloid Fibrils ◽  
Lipid Membrane ◽  
Hydrophobic Interactions ◽  
Membrane Integrity ◽  
Lipid Vesicles ◽  
Helical Conformation ◽  
Unfolded Protein ◽  
Natively Unfolded Protein ◽  
Natively Unfolded

The deposition of α-syn (α-synuclein) as amyloid fibrils and the selective loss of DA (dopamine) containing neurons in the substantia nigra are two key features of PD (Parkinson's disease). α-syn is a natively unfolded protein and adopts an α-helical conformation upon binding to lipid membrane. Oligomeric species of α-syn have been proposed to be the pathogenic species associated with PD because they can bind lipid membranes and disrupt membrane integrity. DA is readily oxidized to generate reactive intermediates and ROS (reactive oxygen species) and in the presence of DA, α-syn form of SDS-resistant soluble oligomers. It is postulated that the formation of the α-syn:DA oligomers involves the cross-linking of DA-melanin with α-syn, via covalent linkage, hydrogen and hydrophobic interactions. We investigate the effect of lipids on DA-induced α-syn oligomerization and studied the ability of α-syn:DA oligomers to interact with lipids vesicles. Our results show that the interaction of α-syn with lipids inhibits the formation of DA-induced α-syn oligomers. Moreover, the α-syn:DA oligomer cannot interact with lipid vesicles or cause membrane permeability. Thus, the formation of α-syn:DA oligomers may alter the actions of α-syn which require membrane association, leading to disruption of its normal cellular function.

scholarly journals Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021 ◽  
Vol 14 (10) ◽  
pp. 1062
Author(s):  
Tomasz Róg ◽  
Mykhailo Girych ◽  
Alex Bunker
Keyword(s):  
Molecular Dynamics ◽  
Drug Design ◽  
Active Site ◽  
Lipid Membranes ◽  
Md Simulation ◽  
Lipid Membrane ◽  
Pharmaceutical Research ◽  
Specific Protein ◽  
Design Tool ◽  
Drug Molecules

We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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