Magnetic nanoparticle-facilitated rapid mass production of high affinity polymeric materials (nanoMIPs) for protein recognition and biosensing.

Molecularly imprinted polymers (MIPs) have been investigated extensively for broad applications in diagnostics, imaging and therapeutics due to their antibody-like specificity, high stability, and low-cost and rapid production when compared with biological antibodies. Yet, their wide-scale adoption and commercial viability are limited due to low yields and relatively lengthy preparations of current methods. We report the novel application of protein-functionalised magnetic nanoparticles (MNPs) to enable the rapid mass production of nanoMIPs for protein recognition.

LPS and Conditioned Medium Enhance the Release of a Low Molecular Weight, Transcriptionally Active, Fragment of Glycogen Synthase-3 Kinase in IMR-32 Cell Line.

Background: Glycogen synthase-3 kinase (GSK3) is one of the major contributors of tau hyperphosphorylation linked to neurofibrillary tangles in Alzheimer's disease (AD).

Objective: To determine a mechanism of GSK-3β activation by two periodontal bacteria consistently confirmed in AD autopsied brains.

Methods: FDC381 and ATCC10301 conditioned media were collected.

Bacterial susceptibility and resistance to modelin-5.

Modelin-5 (M5-NH) killed with a minimum lethal concentration (MLC) of 5.86 μM and strongly bound its cytoplasmic membrane (CM) with a of 23.5 μM.

Aerosolizable Lipid-Nanovesicles Encapsulating Voriconazole Effectively Permeate Pulmonary Barriers and Target Lung Cells.

The entire world has recently been witnessing an unprecedented upsurge in microbial lung infections. The major challenge encountered in treating the same is to ensure the optimum drug availability at the infected site. Aerosolization of antimicrobials, in this regard, has shown immense potential owing to their localized and targeted effect.

PEGylation enhances the antibacterial and therapeutic potential of amphibian host defence peptides.

Aurein 2.1, aurein 2.6 and aurein 3.

Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima: Their Origins, Mechanisms of Action and Potential Applications.

A number of disorders and diseases are associated with conditions of high pH, and many conventional antibiotics lose their efficacy under these pH conditions, generating a need for novel antimicrobials. A potential solution to fulfill this need is Antimicrobial Peptides (AMPs) with high pH optima. This review shows that a variety of anionic and cationic AMPs with this pH dependency are produced by creatures across the eukaryotic kingdom, including rabbits, cattle, sheep, fish, crabs and frog.

Evaluation of acrylamide-based molecularly imprinted polymer thin-sheets for specific protein capture-a myoglobin model.

We evaluate a series of thin-sheet hydrogel molecularly imprinted polymers (MIPs), using a family of acrylamide-based monomers, selective for the target protein myoglobin (Mb). The simple production of the thin-sheet MIP offers an alternative biorecognition surface that is robust, stable and uniform, and has the potential to be adapted for biosensor applications. The MIP containing the functional monomer-hydroxymethylacrylamide (NHMAm), produced optimal specific rebinding of the target protein (Mb) with 84.

Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum.

Here the hypothesis that linearized esculentin 2EM (E2EM-lin) from Glandirana emeljanovi possesses pH dependent activity is investigated. The peptide showed weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM) but potent efficacy towards Gram-positive bacteria (MLCs ≤ 6.

Flow Linear Dichroism of Protein-Membrane Systems.

Linear dichroism (LD) is the differential absorbance of light polarized parallel and perpendicular to an orientation direction. Any oriented sample will show a signal in its electronic as well as vibrational transitions. Model membrane small unilamellar vesicles or liposomes provide an oriented system when they are subject to shear flow in a Couette or other type of flow cell.

In Vitro Characterization of Inhalable Cationic Hybrid Nanoparticles as Potential Vaccine Carriers.

In this study, PGA-co-PDL nanoparticles (NPs) encapsulating model antigen, bovine serum albumin (BSA), were prepared via double emulsion solvent evaporation. In addition, chitosan hydrochloride (CHL) was incorporated into the external phase of the emulsion solvent method, which resulted in surface adsorption onto the NPs to form hybrid cationic CHL NPs. The BSA encapsulated CHL NPs were encompassed into nanocomposite microcarriers (NCMPs) composed of l-leucine to produce CHL NPs/NCMPs via spray drying.

Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention.

Background: Incidence of pulmonary aspergillosis is rising worldwide, owing to an increased population of immunocompromised patients. Notable potential of the pulmonary route has been witnessed in antifungal delivery due to distinct advantages of direct lung targeting and first-pass evasion. The current research reports biomimetic surface-active lipid-polymer hybrid (LPH) nanoparticles (NPs) of voriconazole, employing lung-specific lipid, i.

Biophysical studies on the antimicrobial activity of linearized esculentin 2EM.

Linearized esculentin 2 EM (E2EM-lin) from the frog, Glandirana emeljanovi was highly active against Gram-positive bacteria (minimum lethal concentration ≤ 5.0 μM) and strongly α-helical in the presence of lipid mimics of their membranes (>55.0%).

Toward Rational Design of Selective Molecularly Imprinted Polymers (MIPs) for Proteins: Computational and Experimental Studies of Acrylamide Based Polymers for Myoglobin.

Molecularly imprinted polymers (MIPs) have potential as alternatives to antibodies in the diagnosis and treatment of disease. However, atomistic level knowledge of the prepolymerization process is limited that would facilitate rational design of more efficient MIPs. Accordingly, we have investigated using computation and experiment the protein-monomer binding interactions that may influence the desired specificity.

Biophysical investigation into the antibacterial action of modelin-5-NH.

Modelin-5-CONH2 (M5-NH2) is a synthetic antimicrobial peptide, which was found to show potent activity against Bacillus subtilis (minimum lethal concentration = 8.47 μM) and to bind strongly to membranes of the organism (Kd = 10.44 μM).

Measurements of ultrasonic deterrents and an acoustically branded hairdryer: Ambiguities in guideline compliance.

Acoustic radiation from three commercial pest deterrents and two hair dryers were measured in an anechoic chamber. The deterrents were chosen because the frequency range at which they emit the most energy is either in the very high-frequency sound band (11.2-17.

An Atlas of Anionic Antimicrobial Peptides from Amphibians.

Anionic antimicrobial peptides (AAMPs) with net charges ranging from -1 to -8 have been identified in frogs, toads, newts and salamanders across Africa, South America and China. Most of these peptides show antibacterial activity and a number of them are multifunctional, variously showing antifungal activity, anticancer action, neuropeptide function and the ability to potentiate conventional antibiotics. Antimicrobial mechanisms proposed for these AAMPs, include toroidal pore formation and the Shai-Huang-Matsazuki model of membrane interaction along with pH dependent amyloidogenesis and membranolysis via tilted peptide formation.

Investigations into the potential anticancer activity of Maximin H5.

Here we report the first major example of anionic amphibian host defence peptides (HDPs) with anticancer activity. Maximin H5 (MH5N) is a C-terminally amidated, anionic host defence peptide from toads of the Bombina genus, which was shown to possess activity against the glioma cell line, T98G (EC = 125 μM). The peptide adopted high levels of α-helical structure (57.

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents.

Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known.

Functional foldamers that target bacterial membranes: The effect of charge, amphiphilicity and conformation.

By varying the molecular charge, shape and amphiphilicity of a series of conformationally distinct diarylureas it is possible to control the levels of phospholipid membrane lysis using membranes composed of bacterial lipid extracts. From the data obtained, it appears as though the lysis activity observed is not due to charge, conformation or amphiphilicity in isolation, but that surface aggregation, H-bonding and other factors may also play a part. The work provides evidence that this class of foldamer possesses potential for optimisation into new antibacterial agents.

Low pH Enhances the Action of Maximin H5 against Staphylococcus aureus and Helps Mediate Lysylated Phosphatidylglycerol-Induced Resistance.

Maximin H5 (MH5) is an amphibian antimicrobial peptide specifically targeting Staphylococcus aureus. At pH 6, the peptide showed an improved ability to penetrate (ΔΠ = 6.2 mN m(-1)) and lyse (lysis = 48%) Staphylococcus aureus membrane mimics, which incorporated physiological levels of lysylated phosphatidylglycerol (Lys-PG, 60%), compared to that at pH 7 (ΔΠ = 5.

Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action.

It is becoming increasingly clear that plants ranging across the plant kingdom produce anionic host defence peptides (AHDPs) with potent activity against a wide variety of human cancers cells. In general, this activity involves membrane partitioning by AHDPs, which leads to membranolysis and / or internalization to attack intracellular targets such as DNA. Several models have been proposed to describe these events including: the toroidal pore and Shai-Matsuzaki-Huang mechanisms but, in general, the mechanisms underpinning the membrane interactions and anticancer activity of these peptides are poorly understood.

The effect of amidation on the behaviour of antimicrobial peptides.

Aurein 2.6-COOH and aurein 3.1-COOH were studied along with their naturally occurring C-terminally amidated analogues.

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers.

In this study, Taguchi design was used to determine optimal parameters for the preparation of bovine serum albumin (BSA)-loaded nanoparticles (NPs) using a biodegradable polymer poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL). NPs were prepared, using BSA as a model protein, by the double emulsion evaporation process followed by spray-drying from leucine to form nanocomposite microparticles (NCMPs). The effect of various parameters on NP size and BSA loading were investigated and dendritic cell (DC) uptake and toxicity.

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles.

Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immunocompromised, the very young and the old, and remains one of the leading causes of death. A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S.

Prediction of Peptide and Protein Propensity for Amyloid Formation.

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem.