Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides.

Short-cationic alpha-helical antimicrobial peptides (SCHAMPs) are promising candidates to combat the growing global threat of antimicrobial resistance. They are short-sequenced, selective against bacteria, and have rapid action by destroying membranes. A full understanding of their mechanism of action will provide key information to design more potent and selective SCHAMPs.

Anion Competition at Positively Charged Surfactant Monolayers.

Interactions of anions with hydrophobic surfaces of proteins and water-soluble polymers depend on the ability of the ions to shed their hydration shells. At positively charged surfactant monolayers, the interactions of anions are less well understood. Due to the interplay of electrostatic surface forces, hydration effects, and ion-ion interactions in the electrostatic double layer, a comprehensive microscopic picture remains elusive.

Simulations reveal that antimicrobial BP100 induces local membrane thinning, slows lipid dynamics and favors water penetration.

BP100, a short antimicrobial peptide, produces membrane perturbations that depend on lipid structure and charge, salts presence, and peptide/lipid molar ratios. As membrane perturbation mechanisms are not fully understood, the atomic scale nature of peptide/membrane interactions requires a close-up view analysis. Molecular Dynamics (MD) simulations are valuable tools for describing molecular interactions at the atomic level.

Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity.

In a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformation upon interaction with membranes and increases membrane permeability.

Dehydration Determines Hydrotropic Ion Affinity for Zwitterionic Micelles.

Specific ion effects in zwitterionic micelles, especially for anions, are evident in reaction kinetics, zeta potential, and critical micelle concentration measurements. However, anion adsorption to zwitterionic micelles does not produce significant changes in shape, aggregation number, or interfacial hydration. Here we used molecular dynamics simulation of systems containing sulfobetaine zwitterionic micelles of -dodecyl-,-dimethyl-3-ammonio-1-propanesulfonate (DPS) and nine different salts to explore ion adsorption in terms of group dehydration.

Characterization of phospholipid vesicles containing lauric acid: physicochemical basis for process and product development.

Lauric acid (LAH) strongly inhibits the growth of acne-causing bacteria. LAH is essentially water-insoluble and the solubility of laurate (LA) salts are medium and temperature dependent. Hence, LAH/LA preparations are difficult to formulate.

Binding and Flip as Initial Steps for BP-100 Antimicrobial Actions.

BP100 is a short antimicrobial peptide and can also act as a molecule-carrier into cells. Like with other antimicrobial peptides, the precise mechanism of membrane disruption is not fully understood. Here we use computer simulations to understand, at a molecular level, the initial interaction between BP100 and zwitterionic/negatively charged model membranes.

Specific Ion Effects on Zwitterionic Micelles Are Independent of Interfacial Hydration Changes.

Zwitterionic micelles adsorb anions and several techniques were used to determine the specificity of this interaction. Although at a lower intensity, this adsorption can be compared to those observed in cationic micelles, which showed that interfacial dehydration is a fundamental property for the geometry and size of micelles. Because there is no information on the interfacial hydration of zwitterionic micelles, we used dielectric relaxation spectroscopy (DRS) together with molecular dynamics (MD) simulations to evaluate the importance of surface dehydration promoted by the binding of anions at the micellar interface (sodium bromide, sodium methanesulfonate, sodium trifluoroacetate, and sodium triflate) in N-dodecyl- N, N-dimethyl-3-ammonio-1-propanesulfonate (DPS) micelles.

Synthesis, biophysical and functional studies of two BP100 analogues modified by a hydrophobic chain and a cyclic peptide.

Antimicrobial peptides (AMPs) work as a primary defense against pathogenic microorganisms. BP100, (KKLFKKILKYL-NH), a rationally designed short, highly cationic AMP, acts against many bacteria, displaying low toxicity to eukaryotic cells. Previously we found that its mechanism of action depends on membrane surface charge and on peptide-to-lipid ratio.

Ion dehydration controls adsorption at the micellar interface: hydrotropic ions.

The properties of ionic micelles depend on the nature of the counterion, and these effects become more evident as the ion adsorption at the interface increases. Prediction of the relative extent of ion adsorption is required for rational design of ionic micellar aggregates. Unlike the well understood adsorption of monatomic ions, the adsorption of polyatomic ions is not easily predicted.

Counting ions and other nucleophiles at surfaces by chemical trapping.

The interfaces of membranes and other aggregates are determined by the polarity, electrical charge, molecular volume, degrees of motional freedom and packing density of the head groups of the amphiphiles. These properties also determine the type of bound ion (ion selectivity) and its local density, i.e.

Molecular Dynamics Simulations of the Initial-State Predict Product Distributions of Dediazoniation of Aryldiazonium in Binary Solvents.

The dediazoniation of aryldiazonium salts in mixed solvents proceeds by a borderline SN1 and SN2 pathway, and product distribution should be proportional to the composition of the solvation shell of the carbon attached to the -N2 group (ipso carbon). The rates of dediazoniation of 2,4,6-trimethylbenzenediazonium in water, methanol, ethanol, propanol, and acetonitrile were similar, but measured product distributions were noticeably dependent on the nature of the water/cosolvent mixture. Here we demonstrated that solvent distribution in the first solvation shell of the ipso carbon, calculated from classical molecular dynamics simulations, is equal to the measured product distribution.

Scientists raise alarms about fast tracking of transoceanic canal through Nicaragua.

Seeking economic growth and job creation to tackle the nation's extreme poverty, the Nicaraguan government awarded a concession to build an interoceanic canal and associated projects to a recently formed Hong Kong based company with no track record or related expertise. This concession was awarded without a bidding process and in advance of any feasibility, socio-economic or environmental impact assessments; construction has begun without this information. The 278 km long interoceanic canal project may result in significant environmental and social impairments.

Sodium triflate decreases interaggregate repulsion and induces phase separation in cationic micelles.

Dodecyltrimethylammonium triflate (DTATf) micelles possess lower degree of counterion dissociation (α), lower hydration, and higher packing of monomers than other micelles of similar structure. Addition of sodium triflate ([NaTf] > 0.05 M) to DTATf solutions promotes phase separation.

Peptide:lipid ratio and membrane surface charge determine the mechanism of action of the antimicrobial peptide BP100. Conformational and functional studies.

The cecropin-melittin hybrid antimicrobial peptide BP100 (H-KKLFKKILKYL-NH2) is selective for Gram-negative bacteria, negatively charged membranes, and weakly hemolytic. We studied BP100 conformational and functional properties upon interaction with large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs, containing variable proportions of phosphatidylcholine (PC) and negatively charged phosphatidylglycerol (PG). CD and NMR spectra showed that upon binding to PG-containing LUVs BP100 acquires α-helical conformation, the helix spanning residues 3-11.

Chimeric proteins combining phosphatase and cellulose-binding activities: proof-of-concept and application in the hydrolysis of paraoxon.

Phosphatases for organophosphate degradation and carbohydrate-binding domains (CBMs) have potential biotechnological applications. As a proof-of-concept, a soluble chimeric protein that combines acid phosphatase (AppA) from Escherichia coli and a CBM from Xanthomonas axonopodis pv. citri (AppA-CBM) was produced in E.

Molecular dynamics shows that ion pairing and counterion anchoring control the properties of triflate micelles: a comparison with triflate at the air/water interface.

Micellar properties of dodecyltrimethylammonium triflate (DTA-triflate, DTATf) are very different from those of DTA-bromide (DTAB). DTATf aggregates show high aggregation numbers (Nagg), low degree of counterion dissociation (α), disk-like shape, high packing, ordering, and low hydration. These micellar properties and the low surface tension of NaTf aqueous solutions point to a high affinity of Tf(-) to the micellar and air/water interfaces.

Dielectric relaxation spectroscopy shows a sparingly hydrated interface and low counterion mobility in triflate micelles.

The properties of ionic micelles are affected by the nature of the counterion. Specific ion effects can be dramatic, inducing even shape and phase changes in micellar solutions, transitions apparently related to micellar hydration and counterion binding at the micellar interface. Thus, determining the hydration and dynamics of ions in micellar systems capable of undergoing such transitions is a crucial step in understanding shape and phase changes.

Effect of counterions on the shape, hydration, and degree of order at the interface of cationic micelles: the triflate case.

Specific ion effects in surfactant solutions affect the properties of micelles. Dodecyltrimethylammonium chloride (DTAC), bromide (DTAB), and methanesulfonate (DTAMs) micelles are typically spherical, but some organic anions can induce shape or phase transitions in DTA(+) micelles. Above a defined concentration, sodium triflate (NaTf) induces a phase separation in dodecyltrimethylammonium triflate (DTATf) micelles, a phenomenon rarely observed in cationic micelles.

Interfacial concentrations of chloride and bromide in zwitterionic micelles with opposite dipoles: experimental determination by chemical trapping and a theoretical description.

Interfacial concentrations of chloride and bromide ions, with Li(+), Na(+), K(+), Rb(+), Cs(+), trimethylammonium (TMA(+)), Ca(2+), and Mg(2+) as counterions, were determined by chemical trapping in micelles formed by two zwitterionic surfactants, namely N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS) and hexadecylphosphorylcholine (HDPC) micelles. Appropriate standard curves for the chemical trapping method were obtained by measuring the product yields of chloride and bromide salts with 2,4,6-trimethyl-benzenediazonium (BF(4)) in the presence of low molecular analogs (N,N,N-trimethyl-propane sulfonate and methyl-phosphorylcholine) of the employed surfactants. The experimentally determined values for the local Br(-) (Cl(-)) concentrations were modeled by fully integrated non-linear Poisson Boltzmann equations.

Effects of micelles and vesicles on the oximolysis of p-nitrophenyl diphenyl phosphate: A model system for surfactant-based skin-defensive formulations against organophosphates.

The rates of oximolysis of p-nitrophenyl diphenyl phosphate (PNPDPP) by Acetophenoxime; 10-phenyl-10-hydroxyiminodecanoic acid; 4-(9-carboxynonanyl)-1-(9-carboxy-1-hydroyiminononanyl) benzene; 1-dodecyl-2-[(hydroxyimino)methyl]-pyridinium chloride (IV) and N-methylpyridinium-2-aldoxime chloride were determined in micelles of N-hexadecyl-N,N,N-trimethylammonium chloride (CTAC), N-hexadecyl-N,N-dimethylammonium propanesulfonate and dioctadecyldimethylammonium chloride (DODAC) vesicles. The effects of CTAC micelles and DODAC vesicles on the rates of oxymolysis of O,O-Diethyl O-(4-nitrophenyl) phosphate (paraoxon) by oxime IV were also determined. Analysis of micellar and vesicular effects on oximolysis of PNPDPP, using pseudophase or pseudophase with explicit consideration of ion exchange models, required the determination of the aggregate's effects on the pK(a) of oximes and on the rates of PNPDPP hydrolysis.

Decarboxylation of 6-nitrobenzisoxazole-3-carboxylate in mixed micelles of zwitterionic and positively charged surfactants.

The rate of decarboxylation of 6-nitrobenzisoxazole-3-carboxylate, NBOC, was determined in micelles of N-hexadecyl-N,N,N-trimethylammonium bromide or chloride (CTAB or CTAC), N-hexadecyl-N,N-dimethyl-3-ammonium-1-propanesulfonate (HPS), N-dodecyl-N,N-dimethyl-3-ammonium-1-propanesulfonate (DPS), N-dodecyl-N,N,N-trimethylammonium bromide (DTAB), hexadecylphosphocholine (HPC), and their mixtures. Quantitative analysis of the effect on micelles on the velocity of NBOC decarboxylation allowed the estimation of the rate constants in the micellar pseudophase, k(m), for the pure surfactants and their mixtures. The extent of micellar catalysis for NBOC decarboxylation, expressed as the ratio k(m)/k(w), where k(w) is the rate constant in water, varied from 240 for HPS to 62 for HPC.

Thiolysis and alcoholysis of phosphate tri- and monoesters with alkyl and aryl leaving groups. An ab initio study in the gas phase.

Phosphate esters are important compounds in living systems. Their biological reactions with alcohol and thiol nucleophiles are catalyzed by a large superfamily of phosphatase enzymes. However, very little is known about the intrinsic reactivity of these nucleophiles with phosphorus centers.

Plant uncoupling mitochondrial proteins.

Uncoupling proteins (UCPs) are membrane proteins that mediate purine nucleotide-sensitive free fatty acid-activated H(+) flux through the inner mitochondrial membrane. After the discovery of UCP in higher plants in 1995, it was acknowledged that these proteins are widely distributed in eukaryotic organisms. The widespread presence of UCPs in eukaryotes implies that these proteins may have functions other than thermogenesis.