Identification and design of antimicrobial peptides for therapeutic applications

Indiscriminate use of antibiotics has led to a rapid increase of antibiotic resistance among microbes which has increased the need to develop novel antimicrobial agents to fight various infectious diseases. Peptide antibiotics signify a novel class of therapeutic agents and have been isolated from a wide variety of multi-cellular organisms. Peptide antibiotics have shown broad-spectrum antimicrobial activity and they not only kill different bacteria, but also kill various fungi, parasites, protozoans and cancerous cells. Peptides bear several properties that make them particularly attractive such as their small size, rapid activity and a low chance for development of resistance. Because of these distinct properties, the focus for research on antimicrobial peptides has increased tremendously in the recent years. Despite their potential, only selected cationic antimicrobial peptides have been able to enter in clinical trials. Therefore, there is a pressing need to develop new approaches to identify novel antimicrobial peptide therapeutics replacing conventional antibiotics. Recent findings strongly suggest that one can design a new generation of antimicrobials peptides with a wide range of systemic and topical applications against bacterial infections. In this review, we focus on the identification and design of novel antimicrobial peptides for therapeutic applications based on different approaches and strategies. This review also highlights some recent advances in the study of the molecular basis of anti-microbial activity in these peptides, their current pharmacological and clinical development and future directions and applications.     

Effect of high hydrostatic pressure on seed germination,microbial quality,anatomy–morphology and physiological characteristics of garden cress (Lepidium sativum) seedlings

High hydrostatic pressure is a non-thermal food processing technology that is found to increase the percentage of germination, decrease the germination time and improve the microbial quality of seeds. In this study, pressures of 100–400 MPa for 10 min at 30°C are used to compare the percentage of germination, the microbial quality of seeds, chlorophyll a and b, and total phenolic compounds concentrations in seedlings, and the anatomy–morphology characteristics of garden cress. Enhanced reductions of total aerobic mesophilic bacteria, total and fecal coliforms, and yeast and mould populations in seeds were observed, especially at 300 MPa. In addition, the percentage of germination, chlorophyll content and phenolic compounds concentrations, fresh and dry weights, and hypocotyl lengths of the seedlings are higher than those of all samples, where the percentage of germination is equal to controls but higher than other samples, and radicula length is lower than controls but higher than others.     

Effect of high hydrostatic pressure on the profile of proteins extracted from Betula pendula pollens

High hydrostatic pressure (HHP) has high success potential in pollen protein extraction, but its effect on pollen protein profiles has not been studied yet. The aim of this study is to put forward whether HHP processing causes a change in the protein profiles extracted from pollens or not. In this study, proteins extracted from Betula pendula pollens were studied at 100, 200 and 300?MPa at room temperature for 5?min. In addition, the efficiency of three different extraction solvents, namely phosphate buffer saline (PBS) buffer pH 7.5, trichloroacetic acid–acetone and Tris–HCl buffer pH 8.8, was also observed, and the results were compared with the conventional pollen protein extraction procedure. As a result, it is concluded that 200?MPa for 5?min has extracted similar amounts of protein compared with the conventional extraction method which lasted for 24?h, which lasted for 24 h. On the other hand, the application time for 200 MPa for 5 min is extremely shorter when it is compared to the conventional extraction method.     

Metabolic profile of dystrophic mdx mouse muscles analyzed with in vitro magnetic resonance spectroscopy (MRS)

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy characterized by progressive and irreversible degeneration of the muscles. The mdx mouse is the classical animal model for DMD, showing similar molecular and protein defects. The mdx mouse, however, does not show significant muscle weakness, and the diaphragm muscle is significantly more degenerated than skeletal muscles. In this work, (1)H magnetic resonance spectroscopy (MRS) was used to study the metabolic profile of quadriceps and diaphragm muscles from mdx and control mice. Using principal components analysis (PCA), the animals were separated into groups according to age and lineages. The classification was compared to histopathological analysis. Among the 24 metabolites identified from the nuclear MR spectra, only 19 were used by the PCA program for classification purposes. These can be important key biomarkers associated with the progression of degeneration in mdx muscles and with natural aging in control mice. Glutamate, glutamine, succinate, isoleucine, acetate, alanine and glycerol were increased in mdx samples as compared to control mice, in contrast to carnosine, taurine, glycine, methionine and creatine that were decreased. These results suggest that MRS associated with pattern recognition analysis can be a reliable tool to assess the degree of pathological and metabolic alterations in the dystrophic tissue, thereby affording the possibility of evaluation of beneficial effects of putative therapies.     

Cooperative and diminutive interplay between the sodium bonding with hydrogen and dihydrogen bondings in ternary complexes of NaC3N with HMgH and HCN (HNC)

Ternary complexes of NaC₃N with HMgH and HCN (HNC) are connected by sodium, hydrogen and dihydrogen bonds. Molecular geometries and interaction energies of dyads and triads are investigated at the MøllerPlesset perturbation theory of the second order/aug-cc-pVDZ computational level. Particular attention is paid to parameters, such as cooperative energies and many-body interaction energies. Triads with the HMgH molecule located at the end of the chain show an energetic cooperativity ranging between ?2.13 and ?10.53 kJ mol^?1. When the HMgH molecule is located in the middle, the obtained cluster is diminutive with an energetic effect with values 4.39 and 6.77 kJ mol^?1. The electronic properties of the complexes are analysed using parameters derived from the atoms in molecules methodology. Based on the energy decomposition analysis, it can be seen that the stabilities of the complexes are predicted to be attributable mainly to electrostatic effects.     

Novel In-Situ NanoEmulGel (NEG) of Azithromycin with Eugenol for the Treatment of Periodontitis: Formulation Development and Characterization

Journal of Cluster Science - The aim of present study was to develop and evaluate novel in situ nanoemulgel (NEG) of azithromycin (AZM) with eugenol for intra-pocket drug delivery for the treatment...     

Tetra- and Hexavalent Siglec-8 Ligands Modulate Immune Cell Activation

Carbohydrate-binding proteins are generally characterized by poor affinities for their natural glycan ligands, predominantly due to the shallow and solvent-exposed binding sites. To overcome this drawback, nature has exploited multivalency to strengthen the binding by establishing multiple interactions simultaneously. The development of oligovalent structures frequently proved to be successful, not only for proteins with multiple binding sites, but also for proteins that possess a single recognition domain. Herein we present the syntheses of a number of oligovalent ligands for Siglec-8, a monomeric I-type lectin found on eosinophils and mast cells, alongside the thermodynamic characterization of their binding. While the enthalpic contribution of each binding epitope was within a narrow range to that of the monomeric ligand, the entropy penalty increased steadily with growing valency. Additionally, we observed a successful agonistic binding of the tetra- and hexavalent and, to an even larger extent, multivalent ligands to Siglec-8 on immune cells and modulation of immune cell activation. Thus, triggering a biological effect is not restricted to multivalent ligands but could be induced by low oligovalent ligands as well, whereas a monovalent ligand, despite binding with similar affinity, showed an antagonistic effect.     

Physico-Chemical Properties of Deuteriated Compounds. 1st Communication. The molar volume of n-heptane

The molar volumes of mixtures of perdeuteriated and protiated heptane have been measured between -10° and 40° and expressed as a second order polynomial of the weight fraction. The difference in molar volumes of about 0.4 ml/mol decreases with temperature. The possibility of using the density measurement to determine the degree of deuteriation of mixtures of partially deuteriated heptanes was examined. The percent deuteriation calculated by this method deviates systematically from the true values.     

The effect of high hydrostatic pressure on the muscle proteins of rainbow trout (Oncorhynchus mykiss Walbaum) fillets wrapped with chitosan-based edible film during cold storage (4±1°C)

This study was to determine the effects of changes that occurred in the muscle proteins of fresh rainbow trout (Oncorhynchus mykiss) fillets during storage at 4±1°C as a result of packaging in vacuum (C), subject to high pressure after packaging in vacuum high hydrostatic pressue (HHP), packaged in vacuum after wrapping with chitosan film (CFW) and subject to high pressure after wrapping with chitosan-based film and packaged in vacuum (HHP+CFW ). Samples were subjected to SDS-PAGE in four-day intervals and the densitometric analyses of the gels were carried out. According to the results, minor changes were determined in the major bands of the sarcoplasmic and myofibrillar muscle fractions of trouts as a result of HHP application and CFW. The most important change occurred in the myofibrillar muscle fraction as a decrease in the densities of the bands at 200 and 31.4 kDa after HHP application. Similarly, the sarcoplasmic muscle fraction of trout fillet decreased in the densities of the bands at 39.3, 26.6 and 23.3 kDa after HHP application. In addition, it is thought that the bands that occur at 30 kDa in the myofibrillar muscle fraction and at 20.7 kDa at the sarcoplasmic muscle fraction may be related with the degradation of trouts during cold storage.