scholarly journals The Bacteriostatic Activity of 2-Phenylethanol Derivatives Correlates with Membrane Binding Affinity

Membranes ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 254
Author(s):  
Isabel S. Kleinwächter ◽  
Stefanie Pannwitt ◽  
Alessia Centi ◽  
Nadja Hellmann ◽  
Eckhard Thines ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Hydrophobic Interactions ◽  
Bacteriostatic Activity ◽  
Hydrophobic Core ◽  
Membrane Organization ◽  
Primary Alcohols ◽  
Phenyllactic Acid ◽  
Aromatic Alcohols ◽  
The Impact ◽  
Methyl Phenylacetate

The hydrophobic tails of aliphatic primary alcohols do insert into the hydrophobic core of a lipid bilayer. Thereby, they disrupt hydrophobic interactions between the lipid molecules, resulting in a decreased lipid order, i.e., an increased membrane fluidity. While aromatic alcohols, such as 2-phenylethanol, also insert into lipid bilayers and disturb the membrane organization, the impact of aromatic alcohols on the structure of biological membranes, as well as the potential physiological implication of membrane incorporation has only been studied to a limited extent. Although diverse targets are discussed to be causing the bacteriostatic and bactericidal activity of 2-phenylethanol, it is clear that 2-phenylethanol severely affects the structure of biomembranes, which has been linked to its bacteriostatic activity. Yet, in fungi some 2-phenylethanol derivatives are also produced, some of which appear to also have bacteriostatic activities. We showed that the 2-phenylethanol derivatives phenylacetic acid, phenyllactic acid, and methyl phenylacetate, but not Tyrosol, were fully incorporated into model membranes and affected the membrane organization. Furthermore, we observed that the propensity of the herein-analyzed molecules to partition into biomembranes positively correlated with their respective bacteriostatic activity, which clearly linked the bacteriotoxic activity of the substances to biomembranes.

scholarly journals Effect of Essential Oils on Growth Inhibition, Biofilm Formation and Membrane Integrity of Escherichia coli and Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1474
Author(s):  
Andrés Martínez ◽  
Marcela Manrique-Moreno ◽  
Maria C. Klaiss-Luna ◽  
Elena Stashenko ◽  
German Zafra ◽  
...  
Keyword(s):  
Essential Oils ◽  
Lipid Bilayers ◽  
Biofilm Formation ◽  
Method Development ◽  
Membrane Integrity ◽  
Thymus Vulgaris ◽  
Hydrophobic Core ◽  
Synthetic Membranes ◽  
E Coli ◽  
Microdilution Method

Biofilm as a cellular conformation confers survival properties to microbial populations and favors microbial resistance. Here, we investigated the antimicrobial, antibiofilm, antimotility, antihemolytic activity, and the interaction with synthetic membranes of 15 essential oils (EOs) on E. coli ATCC 25922 and S. aureus ATCC 29213. Antimicrobial activity of EOs was determined through microdilution method; development of the biofilm was assessed using the crystal violet assay and SEM microscopy. Results indicate that Lippia origanoides thymol–carvacrol II chemotype (LTC II) and Thymus vulgaris (TV) exhibited a significant antibacterial activity, with MIC values of 0.45 and 0.75 mg/mL, respectively. The percentage of biofilm formation inhibition was greater than 70% at subinhibitory concentrations (MIC50) for LTC II EO. The results demonstrate that these two oils had significantly reduced the hemolytic effect of S. aureus by 54% and 32%, respectively, and the mobility capacity by swimming in E. coli with percentages of decrease of 55% and 47%, respectively. The results show that LTC II and TV EOs can interact with the hydrophobic core of lipid bilayers and alter the physicochemical properties of membranes. The findings suggest that LTC II and TV oils may potentially be used to aid in the treatment of S. aureus and E. coli infections.

Pressure- and temperature-induced unfolding studies: thermodynamics of core hydrophobicity and packing of ribonuclease A

2006 ◽  
Vol 387 (3) ◽  
pp. 285-296 ◽  
Author(s):  
Josep Font ◽  
Antoni Benito ◽  
Joan Torrent ◽  
Reinhard Lange ◽  
Marc Ribó ◽  
...  
Keyword(s):  
Hydrophobic Interactions ◽  
Rnase A ◽  
Van Der Waals Interactions ◽  
Hydrophobic Core ◽  
Experimental Conditions ◽  
Unfolded State ◽  
Different Temperatures ◽  
Methylene Groups ◽  
The Stability ◽  
Core Packing

Abstract In this work we demonstrate that heat and pressure induce only slightly different energetic changes in the unfolded state of RNase A. Using pressure and temperature as denaturants on a significant number of variants, and by determining the free energy of unfolding at different temperatures, we estimated the stability of variants unable to complete the unfolding transition owing to the experimental conditions required for pressure experiments. The overall set of results allowed us to map the contributions to stability of the hydrophobic core residues of RNase A, with the positions most critical for stability being V54, V57, I106 and V108. We also show that the stability differences can be attributed to both hydrophobic interactions and packing density with an equivalent energetic magnitude. The main hydrophobic core of RNase A is tightly packed, as shown by the small-to-large and isosteric substitutions. In addition, we found that large changes in the number of methylene groups have non-additive positive stability interaction energies that are consistent with exquisite tight core packing and rearrangements of van der Waals' interactions in the protein interior, even after drastic deleterious substitutions.

scholarly journals Effect of hydrophobic core on the electrophoresis of a diffuse soft particle

2017 ◽  
Vol 473 (2199) ◽  
pp. 20160942 ◽  
Author(s):  
Partha P. Gopmandal ◽  
S. Bhattacharyya ◽  
H. Ohshima
Keyword(s):  
Hydrophobic Surface ◽  
Weak Field ◽  
Gradual Transition ◽  
Soft Particle ◽  
Hydrophobic Core ◽  
Particle Mobility ◽  
The Core ◽  
Segment Distribution ◽  
Low Charge ◽  
The Impact

Electrophoresis of a diffuse soft particle with a charged hydrophobic core is considered under the weak field and low charge density assumptions. The hydrophobic surface of the core is coated with a diffuse polyelectrolyte layer (PEL) in which a gradual transition of the polymer segment distribution from the impenetrable core to the surrounding electrolyte medium is considered. A mathematical model is adopted to analyse the impact of the core hydrophobicity on the diffuse soft particle electrophoresis. The mobility based on the present model for the limiting cases such as bare colloids with hydrophobic core and soft particles with no-slip rigid cores are in good agreement with the existing results. The presence of PEL charges produces the impact of the core hydrophobicity on the soft particle mobility different from the corresponding bare colloid with hydrophobic surface in an electrolyte medium. The impact of the core hydrophobicity is subtle when the hydrodynamic screening length of the PEL is low. Reversal in mobility can be achieved by tuning the core hydrophobicity for an oppositely charged core and PEL.

scholarly journals β-Cyclodextrin-Poly (β-Amino Ester) Nanoparticles Are a Generalizable Strategy for High Loading and Sustained Release of HDAC Inhibitors

2020 ◽  
Author(s):  
Sauradip Chaudhuri ◽  
Martha Fowler ◽  
Afroz S. Mohammad ◽  
Wenqui Zhang ◽  
Cassandra Baker ◽  
...  
Keyword(s):  
Self Assembly ◽  
Network Architecture ◽  
Hydrophobic Interactions ◽  
Drug Loading ◽  
Aqueous Media ◽  
Nile Red ◽  
High Loading ◽  
Hydrophobic Core ◽  
Amino Ester ◽  
Critical Determinant

<p> Here, we describe a simple, efficient formulation of a novel library of β-cyclodextrin-poly (β-amino ester) networks (CDN) to achieve this goal. We observed that network architecture was a critical determinant of CDN encapsulation of candidate molecules, with a more hydrophobic core enabling effective self-assembly and a PEGylated surface enabling high loading (up to ~30% w/w), effective self assembly of the nanoparticle, and slow release of drug into aqueous media (24 days) for the model <i>HDACi</i> panobinostat. Optimized CDN nanoparticles were taken up by GL261 cells in culture, and released panobinostat was confirmed to be bioactive. Pharmacokinetic analyses demonstrated that panobinostat was delivered to the brainstem, cerebellum, and upper spinal cord following intrathecal administration via cisterna magna injection in healthy mice. We next constructed a library of CDNs to encapsulate various small, hydrophobic, ionizable molecules (panobinostat, quisinostat, dacinostat, givinostat, and bortezomib, camptothecin, nile red, and cytarabine), which yielded important insights into the structural requirements for effective drug loading and CDN self-assembly. Taken in sum, these studies present a novel nanocarrier platform for encapsulation of <i>HDACi</i> via both ionic and hydrophobic interactions, which is an important step toward better treatment of disease via <i>HDACi</i> therapy.</p>

scholarly journals The mechanism of activation of monomeric B-Raf V600E

2021 ◽  
Author(s):  
Ryan C Maloney ◽  
Mingzhen Zhang ◽  
HYUNBUM JANG ◽  
Ruth Nussinov
Keyword(s):  
Hydrophobic Interactions ◽  
Salt Bridge ◽  
Activation Loop ◽  
Wild Type ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Oncogenic Mutations ◽  
In The Wild ◽  
Activation Pathways ◽  
The Impact

Oncogenic mutations in the serine/threonine kinase B-Raf, particularly the V600E mutation, are frequent in cancer, making it a major drug target. Although much is known about B-Raf's active and inactive states, questions remain about the mechanism by which the protein changes between these two states. Here, we utilize molecular dynamics to investigate both wild-type and V600E B-Raf to gain mechanistic insights into the impact of the Val to Glu mutation. The results show that the wild-type and mutant follow similar activation pathways involving an extension of the activation loop and an inward motion of the αC-helix. The V600E mutation, however, destabilizes the inactive state by disrupting hydrophobic interactions present in the wild-type structure while the active state is stabilized through the formation of a salt bridge between Glu600 and Lys507. Additionally, when the activation loop is extended, the αC-helix is able to move between an inward and outward orientation as long as the DFG motif adopts a specific orientation. In that orientation Phe595 rotates away from the αC-helix, allowing the formation of a salt bridge between Lys483 and Glu501. These mechanistic insights have implications for the development of new Raf inhibitors.

scholarly journals Decoding of novel missense TSC2 gene variants using in-silico methods

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Shruthi Sudarshan ◽  
Manoj Kumar ◽  
Punit Kaur ◽  
Atin Kumar ◽  
Sethuraman G. ◽  
...  
Keyword(s):  
Homology Modeling ◽  
Structure Prediction ◽  
Model Building ◽  
Catalytic Domain ◽  
Hydrophobic Interactions ◽  
Core Protein ◽  
Dimensional Structure ◽  
Specific Cell ◽  
Autosomal Dominant Disorder ◽  
The Impact

Abstract Background Mutations in TSC1 or TSC2 gene cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by the formation of non-malignant hamartomas in multiple vital organs. TSC1 and TSC2 gene products form TSC heterodimer that senses specific cell growth conditions to control mTORC1 signalling. Methods In the present study 98 TSC patients were tested for variants in TSC1 and TSC2 genes and 14 novel missense variations were identified. The pathogenecity of these novel variations was determined by applying different bioinformatics tools involving computer aided protein modeling. Results Protein modelling could be done only for ten variants which were within the functional part of the protein. Homology modeling is the most reliable method for structure prediction of a protein. Since no sequence homology structure was available for the tuberin protein, three dimensional structure was modeled by a combination of homology modeling and the predictive fold recognition and threading method using Phyre2 threading server. The best template structures for model building of the TSC1 interacting domain, tuberin domain and GAP domain are the crystal structures of clathrin adaptor core protein, Rap1GAP catalytic domain and Ser/Thr kinase Tor protein respectively. Conclusions In this study, an attempt has been made to assess the impact of each novel missense variant based on their TSC1-TSC2 hydrophobic interactions and its effect on protein function.

scholarly journals Nanoparticle-Lipid Interaction: Job Scattering Plots to Differentiate Vesicle Aggregation from Supported Lipid Bilayer Formation

2018 ◽  
Vol 2 (4) ◽  
pp. 50 ◽  
Author(s):  
Fanny Mousseau ◽  
Evdokia Oikonomou ◽  
Victor Baldim ◽  
Stéphane Mornet ◽  
Jean-François Berret
Keyword(s):  
Lipid Bilayers ◽  
Lipid Vesicles ◽  
Living Cells ◽  
Supported Lipid Bilayers ◽  
Supported Lipid Bilayer ◽  
Mixed Aggregates ◽  
Method Of Continuous Variation ◽  
The Impact ◽  
Analytical Expressions ◽  
Lipid Interaction

The impact of nanomaterials on lung fluids, or on the plasma membrane of living cells, has prompted researchers to examine the interactions between nanoparticles and lipid vesicles. Recent studies have shown that nanoparticle-lipid interaction leads to a broad range of structures including supported lipid bilayers (SLB), particles adsorbed at the surface or internalized inside vesicles, and mixed aggregates. Currently, there is a need to have simple protocols that can readily evaluate the structures made from particles and vesicles. Here we apply the method of continuous variation for measuring Job scattering plots and provide analytical expressions for the scattering intensity in various scenarios. The result that emerges from the comparison between experiments and modeling is that electrostatics play a key role in the association, but it is not sufficient to induce the formation of supported lipid bilayers.

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