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As effective treatment of glioblastoma is still an unmet need, targeted delivery systems for efficient treatment are of utmost interest. Therefore, in this paper, surface modifications with a small peptide c(RGD) or physiological protein (ApoE3) were investigated. Cellular uptake in murine endothelial cells (bEnd.3) and different glioma cells (human U-87 MG, rat F98) was tested to elucidate possible differences and to correlate the uptake to the receptor expression. Different liposomal formulations were measured at 1 and 3 h for three lipid incubation concentrations. We calculated the liposomal uptake saturation S and the saturation half-time t1/2. An up to 9.6-fold increased uptake for ApoE3-modified liposomes, primarily in tumor cells, was found. Contrarily, c(RGD) liposomes showed a stronger increase in uptake in endothelial cells (up to 40.5-fold). The uptake of modified liposomes revealed enormous differences in S and t1/2 when comparing different tumor cell lines. However, for ApoE3-modified liposomes, we proved comparable saturation values (~25,000) for F98 cells and U-87 MG cells despite a 6-fold lower expression of LRP1 in F98 cells and a 5-fold slower uptake rate. Our findings suggest that cellular uptake of surface-modified liposomes depends more on the target structure than the ligand type, with significant differences between cell types of different origins. [ABSTRACT FROM AUTHOR]

Bacterial infections of the respiratory tract cause millions of deaths annually. Several diseases exist wherein (1) bacterial infection is the main cause of disease (e.g., tuberculosis and bacterial pneumonia), (2) bacterial infection is a consequence of disease and worsens the disease prognosis (e.g., cystic fibrosis), and (3) bacteria-triggered inflammation propagates the disease (e.g., chronic obstructive pulmonary disease). Current approaches to combat infections generally include long and aggressive antibiotic treatments, which challenge patient compliance, thereby making relapses common and contributing to the development of antibiotic resistance. Consequently, the proportion of infections that cannot be treated with conventional antibiotics is rapidly increasing, and novel therapies are urgently needed. In this context, antimicrobial peptides (AMPs) have received considerable attention as they may exhibit potent antimicrobial effects against antibiotic-resistant bacterial strains but with modest toxicity. In addition, some AMPs suppress inflammation and provide other host defense functions (motivating the alternative term host defense peptides (HDPs)). However, the delivery of AMPs is complicated because they are large, positively charged, and amphiphilic. As a result of this, AMP delivery systems have recently attracted attention. For airway infections, the currently investigated delivery approaches range from aerosols and dry powders to various self-assembly and nanoparticle carrier systems, as well as their combinations. In this paper, we discuss recent developments in the field, ranging from mechanistic mode-of-action studies to the application of these systems for combating bacterial infections in the airways. [ABSTRACT FROM AUTHOR]

Required metrological tools, such as higher order reference measurements procedures, pure substance and matrix certified reference materials, are established for small well defined molecules. Difficulties still remain in the provision of SI traceable standards in the area of larger biomolecules such as peptides/proteins. The provision of Primary Calibration Reference Services has been identified as a core technical competency for National Measurement Institutes (NMIs). A concept has been elaborated by the Focus Group I on peptide/protein purity for the strategic planning of ongoing Key Comparisons of the Protein Analysis Working Group (PAWG) within the Comité Consultatif pour la Quantité de Matière (CCQM). The assignment of the mass fraction content of high purity peptide/protein materials will be the subject of the CCQM-K115/P55.2 comparison series to directly support NMI services and certified reference materials currently being provided by NMIs. [ABSTRACT FROM AUTHOR]

Honey is a natural product that is used by a large number of people because of its distinctive compositional constituents, which have a considerable impact on its market value. The distinctive combination of amino acids and sugars found in honey's composition, along with its peptide content, could potentially provide several benefits to human health. During the past few years, cutting-edge techniques have been developed and used for the purpose of investigating, identifying, and characterizing peptides that are produced from honey bees. Therefore, the purpose of this review is to examine current trends and technological advancements in the study of honey bee-derived peptides, focusing on innovative and cutting-edge methods. Furthermore, this review explores various attributes of honey and its components, including the honey bee-derived peptide defensin-1. In addition, this review investigates various methods for separating and purifying peptides, as well as the factors that affect these methods. Additionally, defensin-1, a peptide produced by honey bees, is discussed along with its antioxidant and antimicrobial capabilities. In addition, this review focuses on cutting-edge and innovative omic methods used to study honey bee peptides, as well as the significance of artificial intelligence tools in their investigation. Consequently, the review paper delves into various significant obstacles faced by researchers and scientists studying honey bee peptides, while also offering an extensive range of fascinating opportunities and possibilities for future research for those interested in groundbreaking discoveries in this area. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance, particularly the emergence of resistant strains in fungal pathogens, has become a pressing global health concern. Antifungal peptides (AFPs) have shown great potential as a promising alternative therapeutic strategy due to their inherent antimicrobial properties and potential application in combating fungal infections. However, the identification of antifungal peptides using experimental approaches is time-consuming and costly. Hence, there is a demand to propose fast and accurate computational approaches to identifying AFPs. This paper introduces a novel multi-view feature learning (MVFL) model, called AFP-MVFL, for accurate AFP identification, utilizing multi-view feature learning. By integrating the sequential and physicochemical properties of amino acids and employing a multi-view approach, the AFP-MVFL model significantly enhances prediction accuracy. It achieves 97.9%, 98.4%, 0.98, and 0.96 in terms of accuracy, precision, F1 score, and Matthews correlation coefficient (MCC), respectively, outperforming previous studies found in the literature. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) recognizes foreign threats and triggers immune responses by presenting peptides to T cells. Computationally modeling the binding patterns between peptide and HLA is very important for the development of tumor vaccines. However, it is still a big challenge to accurately predict HLA molecules binding peptides. In this paper, we develop a new model TripHLApan for predicting HLA molecules binding peptides by integrating triple coding matrix, BiGRU + Attention models, and transfer learning strategy. We have found the main interaction site regions between HLA molecules and peptides, as well as the correlation between HLA encoding and binding motifs. Based on the discovery, we make the preprocessing and coding closer to the natural biological process. Besides, due to the input being based on multiple types of features and the attention module focused on the BiGRU hidden layer, TripHLApan has learned more sequence level binding information. The application of transfer learning strategies ensures the accuracy of prediction results under special lengths (peptides in length 8) and model scalability with the data explosion. Compared with the current optimal models, TripHLApan exhibits strong predictive performance in various prediction environments with different positive and negative sample ratios. In addition, we validate the superiority and scalability of TripHLApan's predictive performance using additional latest data sets, ablation experiments and binding reconstitution ability in the samples of a melanoma patient. The results show that TripHLApan is a powerful tool for predicting the binding of HLA-I and HLA-II molecular peptides for the synthesis of tumor vaccines. TripHLApan is publicly available at https://github.com/CSUBioGroup/TripHLApan.git. [ABSTRACT FROM AUTHOR]

AbstractPeptides are important components of human nutrition and health, and considered as safe, nontoxic, and easily absorbed potential drugs. Anti-hypoxia peptides are a kind of peptides that can prevent hypoxia or hypoxia damage. In this paper, the sources, preparations, and molecular mechanisms of anti-hypoxia peptides were systemically reviewed. The combination of bioinformatics, chemical synthesis, enzymatic hydrolysis, and microbial fermentation are recommended for efficient productions of anti-hypoxic peptides. The mechanisms of anti-hypoxic peptides include interference with glycolytic process and HIF-1α pathway, mitochondrial apoptosis, and inflammatory response. In addition, bioinformatics analysis, including virtual screening and molecular docking, provides an alternative or auxiliary method for exploring the potential anti-hypoxic activities and mechanisms of peptides. The potential challenges and prospects of anti-hypoxic peptides are also discussed. This paper can provide references for researchers in this field and promote further research and clinical applications of anti-hypoxic peptides in the future. [ABSTRACT FROM AUTHOR]

There has been growing discovery and use of therapeutic peptides in drug delivery and tissue engineering. Peptides are smaller than proteins and can be formulated into drug delivery systems without significant loss of their bioactivity, which remains a concern with proteins. However, the smaller size of peptides has made the controlled release of these bioactive molecules from carriers challenging. Thus, there has been increasing development of carriers to improve the controlled release of peptides by leveraging hydrophobic and electrostatic interactions between the peptide and the carrier. The focus of this review paper is to critically discuss synthetic and natural nanoparticles and microparticles that have been investigated for the controlled delivery of peptides with emphasis on the underlying interactions. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Type II collagen is a homologous super-helical structure consisting of three identical α1(II) chains. It is a major component of animal cartilage, and is widely used in the food industry. Type II collagen can be extracted by acids, salts, enzymes, and via auxiliary methods and can be further hydrolyzed chemically and enzymatically to produce collagen peptides. Recent studies have shown that type II collagen and its polypeptides have good self-assembly properties and important biological activities, such as maintaining cartilage tissue integrity, inducing immune tolerance, stimulating chondrocyte growth and redifferentiation, and providing antioxidant benefits. This review focuses specifically on type II collagen and describes its structure, extraction, and purification, as well as the preparation of type II collagen peptides. In particular, the self-assembly properties and functional activities of type II collagen and collagen peptides are reviewed. In addition, recent research advances in the application of type II collagen and collagen peptides in functional foods, food additives, food coating materials, edible films, and carriers for the food industry are presented. This paper provides more detailed and comprehensive information on type II collagen and peptide for their application. [ABSTRACT FROM AUTHOR]

Proteins are the carriers of biological structure and function, which are involved in almost all the physiological processes in organisms. The qualitative and quantitative analysis of proteins can not only help us understand the mechanisms of life activities, but also screen for the proteins with abnormal expression compared to healthy controls as biomarkers of diseases as well as environmental exposure to harmful substances, thus facilitating to unravel the mechanisms of disease generation and development. Tandem mass spectrometry (MS/MS) is currently the main tool for high-throughput proteomics analysis. It can characterize the proteins by determining the molecular mass of digestion products, locating modification sites, and obtaining sequence information. However, acidic amino acid residues often have a significant impact on the cleavage process of peptides, limiting the performance of MS/MS. For example, for the phosphopeptides containing abundance of negatively charged carboxyl and phosphoryl groups, their ionization is not efficient in the positive mode, and neutral loss is easy to occur during the cleavage process, resulting in a low coverage of product ions in the MS/MS spectra. In this paper, the carboxyl groups from the R group of aspartic acid and glutamic acid as well as the C-terminus of peptide were neutralized using dimethylamine derivatization under mild condition. Accordingly, the fragmentation features of peptides with altered charge properties were studied in collision-induced dissociation (CID) mode. Further, the peptides were labeled using light and heavy isotopic dimethylamine, respectively, thus enabling to verify the features based on the same ion with different labels. The results showed that the precursor ion signal from the derivatized peptide was significantly enhanced compared to that of the native peptide. And, the derived peptides could yield a variety of a, b, y, and z ions, and some reported ions in MS/MS analysis, such as the ion at m/z 129.10/135.14 produced by the peptides with glutamic acid or lysine residue at C-terminus, which facilitating to determine the C-terminal amino acid of protein. While, the peptides proned to lose the derivative groups located at the C-terminus, yielding a series of ions at m/z ［yn-45.06］ or ［yn-73.05] In addition, the neutralization of carboxyl groups could suppress the loss of phosphoryl groups in phosphopeptides to a certain extent, thus improving the resolution efficiency of the MS/MS spectra. Overall, the derivatization method based on carboxyamidation can provide abundant information for the sequence determination and quantitative analysis of peptides due to the altered fragmentation features in CID mode. [ABSTRACT FROM AUTHOR]

Temporins are short peptides secreted by frogs from all over the world. They exert antimicrobial activity, mainly against Gram-positive bacteria, including resistant pathogens; recent studies highlight other possible applications of these peptides as anticancer or antiviral agents. This review is meant to describe the main features of temporins produced by different ranid genera. Due to the abundance of published papers, we focus on the most widely investigated peptides. We report studies on their mechanism of action and three-dimensional structure in model systems mimicking bacterial membranes or in the presence of cells. The design and the antimicrobial activity of peptide analogues is also described, with the aim of highlighting elements that are crucial to improve the bioactivity of peptides while reducing their toxicity. Finally, a short section is dedicated to the studies aimed at applying these peptides as drugs, to produce new antimicrobial materials or in other technological uses. [ABSTRACT FROM AUTHOR]

Disulfide bond in protein is an important post-translational modification and it is extremely essential for stabilizing the three-dimensional structure of proteins, maintaining the correct folded conformation and regulating their biological activities. Therefore, disulfide bonds assignment is of importance to understand life process and to develop protein pharmaceutical. Mass spectrometry technology can serve not only as a means cleaving the disulfide bonds, but also as an analysis tool assigning disulfide bonds connectivity. As a fragmentation means, mass spectrometry has various of MS/MS fragmentation modes. As a detector, it has the advantages of high sensitivity and high accuracy for mass spectrometry information. With these merits, mass spectrometry could fulfill the desire in the characterization of disulfide bonds. This paper summarized the mass spectrometric methods for locating disulfide bonds in proteins or peptides, according to the medium where the disulfide bonds were broken and the cleavage mechanism. Two cleavage mediums-(solution and gas phase) were divided. According to the cleavage mechanism, reduction/oxidation reaction using chemical reagents, electrochemical reduction based on electrode reaction, and post-column reduction were classified, in which disulfide bonds were cleaved in solution and the mass spectrometer was mainly used as an analysis tool. Meanwhile, molecular collision fragmentation including CID and HCD, electrons capture fragmentation (ECD and ETD), photons absorption fragmentation (e.g. MALDI-ISD and UVPD), and cleavage based on ion-ion reactions were summarized, in which disulfide bonds were cleaved in gas phase. For these methods, mass spectrometer was used not only as an analysis tool but also more importantly as a cleavage approach. This review included most disulfide bonds assignment methods and would facilitate bioinformatics-related researchers to choose an appropriate mass spectrometric method. Additionally, at the end of this paper, several new challenges in the field of disulfide bond assignment were put forward such as the characterization of multiple disulfide bonds in a short peptide, insufficient study of the disulfide bond artifacts, and the new methods based on novel instruments like UVPD. Moreover, in terms of methodological study, it would be promoted by the development of the new ionization and fragmentation technique producing new kinds of characteristic ions and corresponding data processing tools emerged in the future. Through this review, it was expected to develop more effective mass spectrometric methods for disulfide bonds characterization. [ABSTRACT FROM AUTHOR]

Obtaining compounds with specificity for certain isoforms of ion channels is a significant problem of curent physiology and pharmacology. In a series of papers, we have shown that the α-hairpinin fold can serve as a template for the rational design of peptide ligands of potassium channels. Here, we used molecular modeling to optimize the structure of the previously obtained Tk-hefu-10 peptide, a selective KV1.3 channel blocker, with a half-maximal inhibitory concentration (IC50) of ≈150 nM. Molecular dynamics simulation of the Tk-hefu-10–KV1.3 complex provided information on the interaction of individual amino acid residues of the peptide and channel, and the analysis of these interactions made it possible to propose amino acid substitutions in the structure of Tk-hefu-10 to increase its affinity. Novel Tk-hefu-12 peptide is a truncated analog of Tk-hefu-10 by one residue with five substitutions; it is characterized by an IC50 value of ≈70 nM against KV1.3. In addition, there are no methionine residues in the structure of Tk-hefu-12, which makes it possible to obtain Tk-hefu peptides using cyanogen bromide. [ABSTRACT FROM AUTHOR]

Studies on peptide-based emulsifiers in the field of foods have progressed rapidly in the last decade, due to the higher anti-oxidative activity, faster adsorption to the interfaces, reduced allergenicity and higher nutritional values, compared to proteins used as emulsifiers. Peptides therefore have the potential for broader applications in emulsion-based foods. This paper provides an update on the current knowledge of the surface behavior of surface-active peptides and peptide assemblies. Factors affecting physical and oxidative stability of peptide-stabilized emulsions and the fabrication and utilization of peptide-associated conjugates in emulsions have also been summarized. The potential applications of peptide-stabilized emulsions in the food industry are finally discussed. Peptides with different primary and secondary structures show different surface behavior. Surface-active peptides with facial amphiphilicity can orient horizontally at the interfaces, while those with half hydrophobic-half hydrophilic residues orient perpendicularly at the interfaces. In addition, peptide assemblies with supermolecular structures can embed in the oil-water interfaces. The long-chain peptides with molecular weights of higher than 5 kDa usually exhibit better emulsifying capacity than short-chain peptides, and many factors (e.g., pH, temperature and ionic strength) can influence the physical stability of peptide-stabilized emulsions. Moreover, the presence of peptides can improve the oxidative stability of emulsions by repulsing or chelating metals. The fabrication of peptides into conjugates with polysaccharides, flavonoids, or phenols can further improve their emulsifying capacity. Finally, peptide-stabilized emulsions have been reported to be used as encapsulation materials or stabilizers/antioxidants in real emulsion-based food systems. • Protein hydrolysis is the mostly used method to prepare emulsifying peptide. • Primary and secondary structures of peptide affect their orientation at interfaces. • Environmental conditions influence the physical and oxidative stability of peptide-stabilized emulsions. • The stability of peptide-stabilized emulsions can be improved by using peptide conjugates. • Peptide-based emulsions can be used in delivery systems and real food systems. [ABSTRACT FROM AUTHOR]

Nonspecific adsorption of non-target components (especially proteins) in food matrix on sensing surfaces deteriorates accuracy and sensitivity of electrochemical sensors, which is a key challenge for food safety sensing. Therefore, electrochemical sensors with antifouling capability of high-protein food matrices are highly desired. In this paper, an efficient and simple antifouling electrochemical aptasensor for tetracycline (TC) analysis was constructed based on a self-designed Y-shaped peptide [CPPPPEK-(RSERSERSE) 2 ] consisting of cysteine as the anchoring segment, polyproline as the supporting segment, and -EK-(RSERSERSE) 2 as antifouling branches. Hydrophilic and electrically neutral amino acid sequence and Y-shaped space structure of the peptide endow the sensing surface with good antifouling performance in protein solutions and diluted milk. Under optimized experiment conditions, the proposed aptasensor can detect TC with a wide linear range (0.01–100 ng mL−1) and a limit of detection of 5.3 pg mL−1 (S/N = 3). The spiked recovery experiments confirmed high accuracy of the aptasensor in diluted milk without other pretreatments (recoveries: 90.96%–95.86%). This strategy offers a valid way to reduce matrix interference, showing a promise to be extended to other sensing systems for different targets. [Display omitted] • An innovative electrochemical aptasensor was developed for TC determination. • It consists of CPPPPEK-(RSERSERSE) 2 and specific aptamer. • The Y-shaped peptide endowed the aptasensor with excellent antifouling ability. • The proposed sensor has satisfactory selectivity, repeatability and stability. [ABSTRACT FROM AUTHOR]

Peptides have been used as components in biological analysis and fabrication of novel sensors due to several reasons, including well-known synthesis protocols, diverse structures, and acting as highly selective substrates for enzymes. Bio-conjugation strategies can provide a simple and efficient way to convert peptide-analyte interaction information into a measurable signal, which can be further used for the manufacture of new peptide-based biosensors. This paper describes the sensitive properties of a peptide-modified graphene oxide screen-printed carbon electrode for accurate and sensitive detection of a natural polyphenol antioxidant compound, namely rosmarinic acid. Glutaraldehyde was chosen as the cross-linking agent because it is able to bind nonspecifically to the peptide. We demonstrated that the strong interaction between the immobilized peptide on the surface of the sensor and rosmarinic acid favors the addition of rosmarinic acid on the surface of the electrode, leading to an efficient preconcentration that determines a high sensitivity of the sensor for the detection of rosmarinic acid. The experimental conditions were optimized using different pH values and different amounts of peptide to modify the sensor surface, so that its analytical performances were optimal for rosmarinic acid detection. By using cyclic voltammetry (CV) as a detection method, a very low detection limit (0.0966 μM) and a vast linearity domain, ranging from 0.1 µM to 3.20 µM, were obtained. The novelty of this work is the development of a novel peptide-based sensor with improved performance characteristics for the quantification of rosmarinic acid in cosmetic products of complex composition. The FTIR method was used to validate the voltammetric method results. [ABSTRACT FROM AUTHOR]

Peptides, short stretches of amino acids or small proteins that occupy a strategic position between proteins and amino acids, are readily accessible by chemical and biological methods. With ideal properties for forming high-affinity and specific interactions with host target proteins, they have established an important niche in the drug development spectrum complementing small molecule and biological therapeutics. Among the most successful biomedicines in use today, peptide-based drugs show great promise. This, coupled with recent advances in synthetic and nanochemical biology, has led to the creation of tailor-made peptide therapeutics for improved biocompatibility. This review presents an overview of the latest research on pathogen-derived, host-cell-interacting peptides. It also highlights strategies for using peptide-based therapeutics that address cellular transport challenges through the introduction of nanoparticles that serve as platforms to facilitate the delivery of peptide biologics and therapeutics for treating various inflammatory diseases. Finally, this paper describes future perspectives, specific pathogen-based peptides that can enhance specificity, efficiency, and capacity in functional peptide-based therapeutics, which are in the spotlight as new treatment alternatives for various diseases, and also presents verified sequences and targets that can increase chemical and pharmacological value. [Display omitted] • Pathogen-derived peptides attractive for the development of novel therapeutic. • Functional peptide-based therapeutics as new treatment for various diseases. • Peptide-based drug development verified can increase chemical and pharmacological value. [ABSTRACT FROM AUTHOR]

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and Kd values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules. [ABSTRACT FROM AUTHOR]

[Display omitted] • Collagen extraction from food waste was reviewed and discussed. • Food waste sources can be from bovine, porcine, aquatic and insect. • Traditional extraction is conducted together saline, acid or enzymatic treatment. • New technologies contain deep eutetic solvent, supercritical fluids extraction etc. • Collagen has functions in repairing of bone, cornea, neuron and hearth. The process of extracting collagen from food waste (CFW) has captured significant attention, due to its promising economic and environmental benefits. With the growing need for collagen in multiple industries, tapping into food waste as a valuable source offers a sustainable approach that tackles resource efficiency and waste reduction simultaneously. This review aims to comprehensively analyze various aspects of collagen extraction from food waste, providing a holistic understanding of its advancements and potential applications. The scope of this analysis includes exploring the structure of collagen, its different types, and the functional implications, they have. Additionally, the different sources of CFW, including bovine, porcine, aquatic, and insect sources were introduced. To provide a detailed view, the paper also covers traditional and advanced extraction methods, along with an examination of industrial technologies, cost economics, feasibility analysis, and the applications and biological activities of CFW peptides/hydrolysates. Recent advancements in extraction technologies have shown promising results in recovering collagen from discarded food. Techniques like deep eutectic solvent, supercritical fluid extraction, extrusion, and ultrasound-assisted extraction have shown potential for abundant yields and sustainability. These methods are scalable for widespread commercial use and have shown favorable outcomes in resource utilization and waste reduction. The diverse biological properties of collagen peptides and hydrolysates make them potential applications in various fields, including food, pharmaceuticals, cosmetics, and the biomedical sector. [ABSTRACT FROM AUTHOR]

Sarcopenia is characterized as an age-related loss of muscle mass that results in negative health consequences such as decreased strength, insulin resistance, slowed metabolism, increased body fat mass, and a substantially diminished quality of life. Additionally, conditions such as high blood sugar are known to further exacerbate muscle degeneration. Skeletal muscle development and regeneration following injury or disease are based on myoblast differentiation. Bioactive peptides are biologically active peptides found in foods that could have pharmacological functions. The aim of this paper was to investigate the effect of decapeptide DI-10 from the potato alcalase hydrolysate on myoblast differentiation, muscle protein synthesis, and mitochondrial biogenesis in vitro. The treatment of C2C12 myoblasts with DI-10 (10 µg/mL) did not induce cell death. DI-10 treatment in C2C12 myoblast cells accelerates the phosphorylation of promyogenic kinases such as ERK, Akt and mTOR proteins in a dose-dependent manner. DI-10 improves myotubes differentiation and upregulates the expression of myosin heavy chain (MyHC) protein in myoblast cells under differentiation medium with high glucose. DI-10 effectively increased the phosphorylation of promyogenic kinases Akt, mTOR, and mitochondrial-related transcription factors AMPK and PGC1α expression under hyperglycemic conditions. Further, decapeptide DI-10 decreased the expression of Murf1 and MAFbx proteins, which are involved in protein degradation and muscle atrophy. Our reports support that decapeptide DI-10 could be potentially used as a therapeutic candidate for preventing muscle degeneration in sarcopenia. [ABSTRACT FROM AUTHOR]

The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a central role in the underlying pathophysiology of migraine. In comparison to the effective triptan class of antimigraine treatments, the CGRP antagonists possess a comparable efficacy but a superior cardiovascular safety profile in patients. This paper describes the development of selective and potent peptidic CGRP antagonist, FE 205030, that has a fast onset of action and an optimal half-life (subcutaneous T max ~ 60 min, and t 1/2 ~ 4.4 h in 80 kg pigs, respectively), which is key to prevention of the progression of debilitating migraine symptoms. The in vivo efficacy of this agent has been established a translational pharmacodynamic model (inhibition of capsaicin-induced increase in skin blood flow) in cynomolgus monkeys and shows maximal inhibitory activity at circulating concentrations of 30-100 nM. Antagonist activity of FE 205030 was characterized on CGRP-induced vasodilation in isolated human mesenteric resistance arteries in an ex vivo isometric myograph study, and FE 205030 effectively blocked CGRP-induced vasodilation with a pA 2 of 9.3 ± 0.1, mean ± standard error. Multispecies allometric scaling and modeling of subcutaneous (SC) effective concentrations indicates that a dose of 10–30 mg/day is sufficient to achieve a drug exposure/target coverage of 8h, which is useful to prevent migraine recurrence in patients. The molecule also possesses appropriate physicochemical properties that allows for a convenient dosing form factor of 1 ml injection volume with a sufficient solubility and acceptable short-term stability, optimal for treatment of acute migraine episodes in patients. Hence, FE 205030 may provide an important fast-acting injectable option for patients suffering from frequent acute migraine episodes, complementary to preventative monoclonal antibodies and oral small molecule CGRP-R antagonist therapies. [ABSTRACT FROM AUTHOR]

The peptide mimicking small extracellular loop of CD82/KAI1 has been reported to inhibit tumor cell migration and metastasis. This provides an evidence that small extracellular loop domain should be important for the function of CD82/KAI1. In this paper, to investigate the structure basis for the function of EC1 mimic peptide, we systematically analyzed the effects of each amino acid residue in EC1 mimic peptide on its bioactivity. We found that the interfering with the folding of secondary structure with proline, a potent breaker of secondary structure, completely abolished the migration and metastasis-inhibitory activity of EC1 mimic peptide. This means that the bioactivity of EC1 mimic peptide was conformation-dependent. Next, we substitute with proline for amino acid residues in the small extracellular ring region of CD82/KAI1 by the site-specific mutations to disrupting secondary structure and detected its effect on the function of CD82/KAI1. The results showed that the disturbing the secondary structure of small extracellular ring completely abolished the migration and metastasis-inhibitory activity of CD82/KAI1. These results further provide direct evidence that the small extracellular ring is an important function region of CD82/KAI1. • Negatively charged polar amino acids weaken the bioactivity of EC1mimic peptide. • Proline can interfer the folding of second structure of EC1mimic peptide. • The bioactivity of EC1mimic peptide is conformation dependent. • Disturbing the second structure of EC1 abolishes CD82′ anti-metastasis function. • Small extracellular ring domain is necessary for metastasis-suppression role of CD82. [ABSTRACT FROM AUTHOR]

Purpose Smart sensors based on graphene field effect transistor (GFET) and biological receptors are regarded as a promising nanomaterial that could be the basis for future generation of low-power, faster, selective real-time monitoring of target analytes and smaller electronics. So, the purpose of this paper is to provide details of sensors based on selective nanocoatings by combining trinitrotoluene (TNT) receptors (Trp-His-Trp) bound to conjugated polydiacetylene polymers on a graphene channel in GFET for detecting explosives TNT.Design/methodology/approach Following an introduction, this paper describes the way of manufacturing of the GFET sensor by using investigation methods for transferring graphene sheet from Cu foil to target substrates, which is functionalized by the TNT peptide receptors, to offer a system which has the capability of answering the presence of related target molecules (TNT). Finally, brief conclusions are drawn.Findings In a word, shortly after graphene discovery, it has been explored with a variety of methods gradually. Because of its exceptional electrical properties (e.g. extremely high carrier mobility and capacity), electrochemical properties such as high electron transfer rate and structural properties, graphene has already showed great potential and success in chemical and biological sensing fields. Therefore, the authors used a biological receptor with a field effect transistor (FET) based on graphene to fabricate sensor for achieving high sensitivity and selectivity that can detect explosive substances such as TNT. The transport property changed compared to that of the FET made by intrinsic graphene, that is, the Dirac point position moved from positive Vg to negative Vg, indicating the transition of graphene from p-type to n-type after annealing in TNT, and the results show the bipolar property change of GFET with the TNT concentration and the possibility to develop a robust, easy-to-use and low-cost TNT detection method for performing a sensitive, reliable and semi-quantitative detection in a wide detection range.Originality/value In this timeframe of history, TNT is a common explosive used in both military and industrial settings. Its convenient handling properties and explosive strength make it a common choice in military operations and bioterrorism. TNT and other conventional explosives are the mainstays of terrorist bombs and the anti-personnel mines that kill or injure more than 15,000 people annually in war-torn countries. In large, open-air environments, such as airports, train stations and minefields, concentrations of these explosives can be vanishingly small – a few parts of TNT, for instance, per trillion parts of air. That can make it impossible for conventional bomb and mine detectors to detect the explosives and save lives. So, in this paper, the authors report a potential solution with design and manufacture of a GFET sensor based on a biological receptor for real-time detection of TNT explosives specifically. [ABSTRACT FROM AUTHOR]

Neoantigen is a protein produced by mutant gene, which is only expressed in tumor cells. It is an ideal target for therapeutic tumor vaccines. Although synthetic long peptide (SLP)-based neoantigen vaccine, DNA-based neoantigen vaccine, and mRNA-based neoantigen vaccine are all in the development stage, they have some inherent shortcomings. Therefore, researchers turned their attention to a new type of "non-coding RNA (ncRNA)", circular RNA (circRNA), for potential better choice. Because of its unique high stability and protein-coding capacity, circRNA is a promising target in the field of neoantigen vaccine. In this paper, we reviewed the feasibility of circRNA encoding neoantigens, summarized the construction process, explained the mechanism of circRNA vaccine in vitro , and discussed the advantages and disadvantages of circRNA vaccine and possible combination with other immunotherapies. • Tumor vaccine is a new direction of cancer prevention and treatment. • Tumor neoantigens are tumor specific proteins and are ideal targets for tumor vaccines. • circRNA can be used as a vector for tumor vaccines because of its ability to encode small peptides. • In this paper, the construction method and application prospect of circRNA vaccine are described in detail. [ABSTRACT FROM AUTHOR]

Hantavirus (HV), a pathogen of animal infectious diseases that poses a threat to humans, has attracted extensive attention. Clinically, HV can cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), between which HFRS is mostly in Eurasia, and HPS is mostly in the Americas. This paper reviews the research progress of small-molecule inhibitors of HV. [ABSTRACT FROM AUTHOR]

Flow injection chromatography (FIC) or sequential injection chromatography (SIC) is a low-pressure liquid chromatography technique that uses flow injection or sequential injection hardware. Due to the constraints of this hardware, the separation resolution is low; often no more than 3–5 components are resolved. We have recently demonstrated the excellent resolving power of narrow open tubular (OT) columns for various biomolecules, and only moderate elution pressures are needed to carry out these separations. In this paper, we incorporate a narrow OT column with FIC and construct an FIC system using a pressure chamber and two injection valves to implement gradient elution. The resultant system not only improves the resolution but also reduces the system cost. When we use the system to separate peptides from trypsin-digested cytochrome C, we can resolve dozens of peptides (with resolutions of 0.5 or greater) at a speed of 12 samples per hour. When we use this system to separate a mixture containing 3 amino acids, we can base-line resolve these compounds at a speed of 1800 sample per hour. Image 1 • Incorporated a NOT column with FI for ultrafast FIC. • Constructed a dual-valve system to perform gradient FIC. • Separation amino acids at a speed of 1800 samples per hour. [ABSTRACT FROM AUTHOR]

• Oxytocin (OT) subserves adaptive physiological, behavioral, and cognitive functions. • Literature synthesis shows chronic OT improves outcomes in different circumstances. • Multiple, interrelated regulatory functions are sensitive to chronic OT. • More systematic and mechanistic research needed to determine therapeutic efficacy. • Attention to interindividual and contextual factors will advance the field. Oxytocin (OT) subserves various physiological, behavioral, and cognitive processes. This paired with the ability to administer OT with minimal and inconsistent side effects has spurred research to explore its therapeutic potential. Findings from single-dose studies indicate that OT administration may be beneficial, at least under certain circumstances. The state of the field, however, is less clear regarding effects from chronic OT administration, which more closely resembles long-term treatment. To address this gap, this review synthesizes existing findings on the use of chronic OT administration in animal and human work. In addition to detailing the effects of chronic OT administration across different functional domains, this review highlights factors that have contributed to mixed findings. Based on this review, a basic framework of interrelated regulatory functions sensitive to chronic OT administration is offered. The paper also identifies future research directions across different contexts, populations, and outcomes, specifically calling for more systematic and standardized research on chronic OT administration in humans to supplement and expand what is currently known from preclinical work. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that the poly-arginine peptide R18 can improve histological and functional outcomes following traumatic brain injury (TBI) in the Sprague–Dawley rat. Since D-enantiomer peptides are often exploited in pharmacology for their increased stability and potency, the present study compared the effects of R18 and its D-enantiomer, R18D, following TBI in the Long-Evans rat. Following a closed-head impact delivered via a weight-drop apparatus, peptide was administered at a dose of 1000 nmol/kg at 30 min after TBI. Treatment with R18D, but not R18 resulted in significant reductions in sensorimotor (p = 0.026) and vestibulomotor (p = 0.049) deficits as measured by the adhesive tape removal and rotarod tests. Furthermore, treatment with R18 and R18D resulted in a significant reduction in brain protein levels of the astrocytic marker, glial fibrillary acidic protein (p = 0.019 and 0.048, respectively). These results further highlight the beneficial effects of poly-arginine peptides in TBI, however additional studies are required to confirm these positive effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • Oral egg white hydrolysate (EWH) improved the plasma peptide-bound amino acids (PAA). • The levels of the plasma PAA was positively related to that of EWH. • Thirty-three egg white-derived peptides were identified from the plasma of rats. • EWH increased the expressions of genes of the clathrin-dependent endocytosis. • EWH transported through the intestine mainly via the clathrin-dependent endocytosis. This paper aimed to investigate the in vivo absorption of egg white hydrolysate (EWH) in rats and the transport route across the intestinal epithelium. Results showed that the level of plasma peptide-bound amino acid (PAA) of the EWH-supplemented rats (EWH-R) was determined to be 2012.18 ± 300.98 μmol/L, 10.72% higher than that of the control group, and was significantly positively correlated to that of EWH. Thirty-three egg white-derived peptides were successfully identified from the plasma of EWH-R, and 20 of them were found in both EWH-R plasma and EWH, indicating that these peptides tend to be absorbed through the intestinal epithelium in intact forms into the blood circulation. In addition, 637 up-regulated and 577 down-regulated genes in Caco-2 cells incubated with EWH were detected by RNA-sequencing and the clathrin-dependent endocytosis was the most enriched pathway in KEGG analysis. EWH significantly increased the mRNA levels of the key genes involved in the clathrin-dependent endocytosis but these changes would be inhibited by the clathrin-dependent endocytosis inhibitor of chlorpromazine. Moreover, the transepithelial transport of EWH across Caco-2 cell monolayers was significantly reduced by chlorpromazine. This study provided molecular-level evidence for the first time that clathrin-dependent endocytosis might be the main transport route of EWH in the intestinal epithelium. [ABSTRACT FROM AUTHOR]

Peptides exhibit various functional properties and bioactivities, and have been widely investigated and used in food area. However, using peptides alone may show some drawbacks, such as the undesirable stability of peptide-stabilized emulsions during storage, and the diminished bioactivities and the occurrence of peptide-induced celiac disease during digestion. The addition of polyphenols may help to solve above issues by the formation of peptide-polyphenol complexes. This paper provides a comprehensive review of covalent and non-covalent interactions between peptides and polyphenols. The influence of such interactions in bioactivity, antimicrobial property, sensitivity (i.e., causing celiac disease), and emulsifying property of peptides is also discussed. Hydrophobic interactions, hydrogen bonds, electrostatic interaction, and van der Waals interactions are the main non-covalent bondings involving in the formation of peptide-polyphenol complexes. The properties of peptides and polyphenols, the ratio of peptide/polyphenol, and the environmental conditions are the main factors influencing such non-covalent interactions. Oxidized peptides or reactive peptide radicals can also interact with polyphenols trough covalent interactions, and the properties of peptides and polyphenols can influence these interactions. In addition, the presence of polyphenols in peptide-polyphenol complexes can show synergetic or subtractive effect on bioactive peptides through various mechanisms. In contrary, the inhibiting effect of polyphenols on the digestion, absorption and recognition of peptides can help to improve the safety of celiac disease-related peptides. Moreover, the formation of peptide-polyphenol complexes can also improve the physical and oxidative stability of peptide-stabilized emulsions. • The impact of forming peptide-polyphenol complexes on the properties of peptides is reviewed. • The peptide-polyphenol complexes can be obtained by covalent or non-covalent bonds. • The presence of polyphenols enhances or diminishes the bioactivities of peptides. • The presence of polyphenols improves the safety of celiac disease-related peptides. • The formation of complexes can also improve the emulsifying properties of peptides. [ABSTRACT FROM AUTHOR]

[Display omitted] • Oral egg white hydrolysate (EWH) improved the plasma peptide-bound amino acids (PAA). • The levels of the plasma PAA was positively related to that of EWH. • Thirty-three egg white-derived peptides were identified from the plasma of rats. • EWH increased the expressions of genes of the clathrin-dependent endocytosis. • EWH transported through the intestine mainly via the clathrin-dependent endocytosis. This paper aimed to investigate the in vivo absorption of egg white hydrolysate (EWH) in rats and the transport route across the intestinal epithelium. Results showed that the level of plasma peptide-bound amino acid (PAA) of the EWH-supplemented rats (EWH-R) was determined to be 2012.18 ± 300.98 μmol/L, 10.72% higher than that of the control group, and was significantly positively correlated to that of EWH. Thirty-three egg white-derived peptides were successfully identified from the plasma of EWH-R, and 20 of them were found in both EWH-R plasma and EWH, indicating that these peptides tend to be absorbed through the intestinal epithelium in intact forms into the blood circulation. In addition, 637 up-regulated and 577 down-regulated genes in Caco-2 cells incubated with EWH were detected by RNA-sequencing and the clathrin-dependent endocytosis was the most enriched pathway in KEGG analysis. EWH significantly increased the mRNA levels of the key genes involved in the clathrin-dependent endocytosis but these changes would be inhibited by the clathrin-dependent endocytosis inhibitor of chlorpromazine. Moreover, the transepithelial transport of EWH across Caco-2 cell monolayers was significantly reduced by chlorpromazine. This study provided molecular-level evidence for the first time that clathrin-dependent endocytosis might be the main transport route of EWH in the intestinal epithelium. [ABSTRACT FROM AUTHOR]

• Two-dimensional separations enable peak purity analysis of pharmaceutical peptides. • Strategy to derive second-dimension gradient conditions. • Preferred gradient conditions discovered by retention modelling. The importance of therapeutic peptides continues to increase in the marketplace for treating a range of diseases including diabetes and obesity. Quality control analyses for these pharmaceutical ingredients usually depends on reversed-phase liquid chromatography, and it is critically important to ensure that no impurities coelute with the target peptide at levels that would compromise the safety or effectiveness of the drug products. This can be challenging due to the broad range of properties of impurities that can be present on one hand (e.g., amino acid substitutions, chain cleavages, etc.), and the similarity of other impurities on the other hand (e.g., d -/ l -isomers). Two-dimensional liquid chromatography (2D-LC) is a powerful analytical tool that is well suited to address this particular problem; the first dimension can be used to detect impurities over a broad range in properties, while the second dimension can be used to focus specifically on those species that might coelute with the target peptide in the first dimension. While hundreds of papers have been published on the use of 2D-LC for proteomics applications, there are very few papers that have focused on its use for characterisation of therapeutic peptides. This paper is the second in a two-part series. In Part I of the series, we studied several different column / mobile phase combinations that could be useful in 2D-LC separations of therapeutic peptides, with a focus on selectivity, peak shape, and complementarity to other combinations, particularly for isomeric peptides under mass spectrometry-friendly conditions (i.e., volatile buffers). In this second part in the series, we describe a strategy to derive second-dimension (2D) gradient conditions that both, ensure elution from the 2D column, and increase the likelihood of resolving peptides with very similar properties. We find that a two-step process yields conditions that place the target peptide in the middle of the 2D chromatogram. This process begins with two scouting gradient elution conditions in the second dimension of a 2D-LC system, followed by building and refining a retention model for the target peptide using a third separation. The process is shown to be generically useful by developing methods for four model peptides, and application to a sample of degraded model peptide to demonstrate its utility for resolving impurities in a real sample. [ABSTRACT FROM AUTHOR]

In this paper, the relationship between protein structure changes and in vitro digestion of preserved egg white (PEW) during pickling was studied. Results showed that as the pickling time increased, moisture content of PEW exhibited a decreasing trend, pH value and hardness of PEW exhibited an increasing trend. Environmental Scanning Electron Microscopy (ESEM) revealed that alkali-treated duck egg white could form a more compact gel network structure during pickling. Transmission Electron Microscopy (TEM) showed that PEW consisted of two sorts of structures, namely fibrillar (from 7th to 21st day) and particulate (from 28th to 42nd day). Fourier Transform Infrared (FTIR) spectroscopy showed that there was an increase in the content of β-sheets and a decrease in the content of α-helices during pickling. Protein digestibility of PEW was highest at day 14 and the lowest at day 42. Moreover, the content of β-sheets was negatively correlated with protein digestibility. Peptides identification using LC-MS/MS highlighted that the number of different peptides were positively correlated with the pickling. The number of unique peptides was negatively correlated with protein digestibility at the end of gastric and intestinal digestion. This study would provide guidance for studying nutritional value and controlling quality of preserved eggs. Unlabelled Image [ABSTRACT FROM AUTHOR]

Zika virus has recently evolved from an obscure mosquito-borne pathogen to an international public health concern. People with Zika virus disease can have indications including mild fever, skin rash, conjunctivitis, muscle pain, malaise or headache. Effective vaccines are needed for controlling and preventing the disease. In the current study, we aim to design the substructure for vaccine against Zika virus by forming antigenic peptide epitope of the disease. Zika peptide loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles have been fabricated in the present work as a potential artificial vaccine. UV and FT-IR Spectrophotometers and ZetaSizer were used for studying the nanoparticles, and Scanning Electron Microscope was used for morphological examination. The nanoparticles (NPs) yield, encapsulation efficiency, the peptide loading capacity were determined and in vitro release of the peptide was studied. Cytotoxic effects of the various concentrations of Zika peptide, blank PLGA nanoparticles and Zika peptide loaded PLGA nanoparticles on ECV304 human epithelial cells were determined via MTT assay. The present paper could be considered as one of the important steps in the use of nanoparticles for constructing the new generation of vaccination systems. [ABSTRACT FROM AUTHOR]

Abstract Centrin is a member of the EF-hand super-family that plays pivotal role in the centrosome duplication and separation. In the present paper, we characterized the properties of metal ions as well as peptide R18-Sfi1p binding to human centrin 1 (HsCen1) by fluorescence spectra and isothermal titration calorimetry (ITC). Four metal ions binding sites on HsCen1 were identified through ITC experiments. The conditional binding constants of the EF-hand domain on HsCen1 with Ca2+ were quantitatively calculated. In reversible manner, Ca2+ can induce HsCen1 self-assembly. In addition, HsCen1 bound with peptide R18-Sfi1p in calcium-dependent with middle-affinity. Phosphorylation at Ser170 weakened interaction HsCen1 with the substrate and removal calcium ions further weakened interactions of the two molecules. Hence, we inferred that centrin initiating downstream peptides may be a double-regulated process by calcium and phosphorylation. These results are of significance for understanding the relationship between PTM and metal regulation. Highlights • The binding constants of the each EF-hand domain on HsCen1 with metal ions were quantitatively calculated. • Introducing the phosphate group at Ser170 on HsCen weakened its binding with peptide of R18-Sfi1p. • HsCen1 binding with R18-Sfi1p was double-regulated by calcium as well as phosphorylation. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Myostatin is a negative regulator of skeletal muscle growth and myostatin inhibitors are promising lead compounds against muscle atrophic disorders such as muscular dystrophy. Previously, we published the first report of synthetic myostatin inhibitory 23-mer peptide 1 , which was identified from a myostatin precursor-derived prodomain protein. Our structure-activity relationship study afforded the potent inhibitory peptide 3. In this paper, we report an investigation of the synthesis of conformationally-constrained cyclic peptide based on the linear peptide 3. To examine the potency of side chain-to-side chain cyclized peptides, a series of disulfide-, lactam- and diester-bridged derivatives were designed and synthesized, and their myostatin inhibitory activities were evaluated. The diester-bridged peptide (11) displayed potent inhibitory activity with an in vitro IC 50 value of 0.26 µM, suggesting that it could serve as a new platform for development of cyclic peptide inhibitors. [ABSTRACT FROM AUTHOR]

Rice bran has been predominantly used in the feed industry, and only recently it has attracted greater attention in terms of human nutrition with increasing knowledge of its bioactivity. A growing interest is the analysis of physiologically active peptides derived from rice bran proteins. In this paper, the bioactivities of rice bran proteins hydrolysates and peptides are reviewed based on recent studies. These enzymatic hydrolysates and peptides exert various biological activities including antioxidant, antidiabetic, anticancer and inhibitory activity for angiotensin converting enzyme (ACE), which may ultimately prevent certain chronic diseases. Nevertheless, these functionalities can be highly associated with their corresponding structural characteristics, in particular specific sequences and molecular weight distribution. This article may facilitate the expansion of the prospective applications of the bioactive peptides in a number of fields and provide some clues of the relationship between peptides structure and functionality for future research. [ABSTRACT FROM AUTHOR]

Purpose Miniaturized smart sensors that can perform sensitive and selective real-time monitoring of target analytes are tremendously valuable for various sensing applications. So, the purpose of this paper is to provide details of sensors based on selective nanocoatings by combining trinitrotoluene (TNT) receptors bound to conjugated polydiacetylene (PDA) polymers with single-walled carbon nanotube field-effect transistors (CNTFETs) for detecting explosives TNT.Design/methodology/approach Following an introduction, this paper describes the way of creating an FET with CNTs, which are functionalized by the peptide based on TNT molecule recognition elements and PDA, to offer a system which has the capability of answering the presence of related target molecules (TNT). Finally, brief conclusions are drawn.Findings Single-wall nanotubes and reduced graphene oxide are interesting materials for creating biosensors of FETs at nanoscale because of unique electrical, mechanical, geometrical and biocompatible properties. Therefore, this sensor is designed and manufactured, and the results of applying TNT to sensor show good sensitivity and selectivity response.Originality/value In this timeframe of history, sensors based on CNTFET are required for different uses, including clinical diagnosis technologies, environmental tests and bioterrorism recognition technologies, that correspond to the military conflicts and terrorism. So, CNTFET sensor design provides real-time detection of TNT explosives. [ABSTRACT FROM AUTHOR]

Antigen-based sensing is recognized as a rapid and sensitive analysis among bioresearch groups. The potential of “on-site” analysis in such devices has been accompanied by some problems. Fabrication of silicon compatible and highly sensitive biosensors has been the center of excessive research within the past few years. In this paper, we report fabrication of two types of sensitive liquid oxide semiconductor (LOS) biosensors using nanostructures. These devices have been manufactured and characterized as immunosensors. These two types of sensors have been produced using different platforms for immobilization of proteins; one based on a functionalized silicon dioxide surface by 3-aminopropyltriethoxysilane (APTES) and another on the basis of using 50-nm amine-modified polystyrene nanobeads. The polystyrene platform not only benefits from its nanosize and high surface to volume ratio but also does not need any new protocol than what is already used for traditional immunosensing system. These sensors measure the change of threshold voltage of the semiconductor inversion inside the capacitor due to the bonding of antibodies to the linked peptides on the surface. Measurements showed that the sensitivity of 50-nm polystyrene-based sensor is much more than the oxide-based one. The nanobeads were then chosen to cover the gate of the ISFET for the amplified sensing. The ISFET devices were biased in a subthreshold region to demonstrate the maximum sensitivity to the accumulated charge on the gate. Repeatable results after different stress tests were obtained, which proves the suitability and reliability of the polystyrene nanobead platform for this application. Finally, a calibration curve has been derived that can be used for real sample measurements. The detection limit of 1.0152 μg/ml was calculated for the fabricated sensor.Graphical abstract [ABSTRACT FROM AUTHOR]

There is a growing need in the industrial sector (health, nutrition and cosmetic) to discover new biomolecules with various physico-chemical and bioactive properties. Various beneficial effects of peptides – notably those produced from protein hydrolysis – are reported in the literature. The antioxidant activity involves various mechanisms, among them metal chelation, studied by UV-visible spectrophotometry. In this paper, we set up an original method of screening metal chelating peptides in a hydrolysate using Surface Plasmon Resonance (SPR) for their antioxidant properties. To date, the empirical approach used several cycles of hydrolysate fractionation and bioactivity evaluation until the isolation of the pure bioactive molecule and its identification. Besides, the detection of metal-chelating peptide is not sensitive enough by spectrophotometry. For the first time, metal chelating peptides were screened in hydrolysates using SPR and a correlation was established between affinity constant determined in SPR and metal chelation capacity determined from UV-visible spectrophotometry. [ABSTRACT FROM AUTHOR]

This paper reports on the LGX fluorometric test for enzymatic MRSA/MSSA detection. It highlights the reasons rhodamines have been overlooked and also strategies to improve the synthesis of rhodamine-peptide conjugates. Evaluation of the LGX test for detection of MRSA/MSSA on surfaces is undertaken in the presence of potentially confounding E. coli and S. epidermidis for the first time. [ABSTRACT FROM AUTHOR]

[Display omitted] • Peptide based dot-blot assay detects AFB1 rapidly, sensitively and is easy-to-use. • Molecular docking of AFB1with human serum albumin generated a specific octapepetide. • Low K d app (323 nM) by indirect ELISA confirmed peptide binding affinity to AFB1. • Dot-blot assay detected AFB1 in food and feed samples and correlated highly to HPLC. • Dot-blot assay is a on-site detection method for safe, healthy food and feed. Aflatoxin B1 (AFB1) is a hepatotoxic and carcinogenic food contaminant. Although on-site paper-based detection is sensitive it depends on expensive antibodies which are difficult to raise against mycotoxins. Here, we rationally designed a high binding octapeptide, N-KSGKSKPR-C peptide for AFB1 detection, by molecular docking, as confirmed by indirect ELISA (K d 323 nM). Further, conjugation of octapeptide with gold nanoparticles (26 nm) permitted its use as a visual detection agent in rapid, sensitive dot-blot assay (LOD 0.39 μg/kg). The assay displayed negligible cross-reactivity with co-contaminating mycotoxins. AFB1 recovery from spiked wheat sample was comparable by dot-blot (78–91 %) and HPLC (65–87 %). Evaluation of dot-blot using certified reference material and 146 food and feed samples showed high correlation R2 = 0.87 with HPLC. The assay displayed high accuracy (91 %), sensitivity (71 %) and specificity (96.5 %). Therefore, the developed dot-blot assay holds promise for monitoring AFB1 contamination in food and feed. [ABSTRACT FROM AUTHOR]

Peptides are a fast growing segment in the pharmaceutical industry. Consequently, the industry and regulatory agencies are increasing their focus on the regulatory path and quality considerations for peptide development and manufacturing. Although most peptides are synthetic, manufactured by solid phase synthesis, nevertheless they are complex molecules with challenging quality and regulatory aspects. This paper provides a structured overview of relevant quality issues for chemically synthesized peptides used as active pharmaceutical ingredients (API) in drug products. It addresses the unique characteristics of peptides pertaining to structural and physicochemical characterization, manufacturing and in process controls, impurities and aggregates arising from manufacturing and storage, along with their potential impact on safety (including immunogenicity) and efficacy of the peptide drug products. [ABSTRACT FROM AUTHOR]

• A supramolecular metallopeptide hydrogel (Supra GHK-Cu) was developed by metal coordination and peptide assembly. • Molecular dynamics simulation indicates the multiple coordination patterns between supramolecular peptides and Cu2+. • Supramolecular metallopeptide showed excellent biostability and wound healing properties. • Supra GHK-Cu exemplifies a successful bio-inspired supramolecular metallopeptide hydrogel. • An alternative strategy to overcome the limitations of traditional bioactive metallopeptides. Inspired by the regulation of protein structure and function by metal ions in life, the role of metal coordination in the folding and assembly of peptides has been gradually studied. However, the construction of bioactive supramolecular metallopeptides with synergism between metal coordination and peptide self-assembly remains challenging. This paper reports a bio-inspired peptide derivative (Supra GHK (glycyl- l -histidyl- l -lysine)) bearing a natural-derived GHK tri-peptide motif, which could self-assemble into supramolecular metallopeptide hydrogel (Supra GHK-Cu) after adding Cu2+. The addition of Cu2+ prompts the allosteric effects on the folded structure of Supra GHK, resulting from the participation of atoms on the backbone of the peptide in the chelation. Cu2+ has a stronger affinity for Supra GHK by bridging two peptide molecules or interacting with one peptide molecule, as confirmed by experimental results and molecular dynamics simulation. Remarkably, due to the formation of supramolecular structures, Supra GHK-Cu possesses excellent resistance against protease degradation. Moreover, it accelerates wound healing more significantly than GHK-Cu by promoting collagen deposition, angiogenesis and cell proliferation. This work not only exemplifies a successful bio-inspired supramolecular metallopeptide hydrogel but also provides a promising alternative strategy to overcome the limitations of traditional bioactive peptides in various biomedical fields. [ABSTRACT FROM AUTHOR]

Phospholipase A 2 (named bitanarin) possessing capability to block nicotinic acetylcholine receptors (nAChRs) was isolated earlier (Vulfius et al., 2011) from puff adder Bitis arietans venom. Further studies indicated that low molecular weight fractions of puff adder venom inhibit nAChRs as well. In this paper, we report on isolation from this venom and characterization of three novel peptides called baptides 1, 2 and 3 that reversibly block nAChRs. To isolate the peptides, the venom of B. arietans was fractionated by gel-filtration and reversed phase chromatography. The amino acid sequences of peptides were established by de novo sequencing using MALDI mass spectrometry. Baptide 1 comprised 7, baptides 2 and 3–10 amino acid residues, the latter being acetylated at the N-terminus. This is the first indication for the presence of such post-translational modification in snake venom proteins. None of the peptides contain cysteine residues. For biological activity studies the peptides were prepared by solid phase peptide synthesis. Baptide 3 and 2 blocked acetylcholine-elicited currents in isolated Lymnaea stagnalis neurons with IC 50 of about 50 μM and 250 μM, respectively. In addition baptide 2 blocked acetylcholine-induced currents in muscle nAChR heterologously expressed in Xenopus oocytes with IC 50 of about 3 μM. The peptides did not compete with radioactive α-bungarotoxin for binding to Torpedo and α7 nAChRs at concentration up to 200 μM that suggests non-competitive mode of inhibition. Calcium imaging studies on α7 and muscle nAChRs heterologously expressed in mouse neuroblastoma Neuro2a cells showed that on α7 receptor baptide 2 inhibited acetylcholine-induced increasing intracellular calcium concentration with IC 50 of 20.6 ± 3.93 μM. On both α7 and muscle nAChRs the suppression of maximal response to acetylcholine by about 50% was observed at baptide 2 concentration of 25 μM, the value being close to IC 50 on α7 nAChR. These data are in accord with non-competitive inhibition as follows from α-bungarotoxin binding experiments. The described peptides are the shortest peptides without disulfide bridges isolated from animal venom and capable to inhibit nAChR by non-competitive way. [ABSTRACT FROM AUTHOR]

Aphids are major insect pests for crops, causing damage by direct feeding and transmission of plant diseases. This paper was completed to discover and characterize a novel insecticidal metabolite against aphids from soil actinobacteria. An insecticidal activity assay was used to screen 180 bacterial strains from soil samples against mustard aphid, Lipaphis erysimi. The bacterial strain H008 showed the strongest activity, and it was identified by the phylogenetic analysis of the 16S rRNA gene and physiological traits as a novel species of genus Streptomyces (named S. laindensis H008). With the bioassay-guided method, the insecticidal extract from S. laindensis H008 was subjected to chromatographic separations. Finally, a novel insecticidal peptide was purified from Streptomyces laindensis H008 against L. erysimi, and it was determined to be S-E-P-A-Q-I-V-I-V-DG- V-D-Y-W by TOF-MS and amino acid analysis. [ABSTRACT FROM AUTHOR]

How to process and analyze MS data to quantify and statistically compare protein abundances in bottom-up proteomics has been an open debate for nearly fifteen years. Two main approaches are generally used: the first is based on spectral data generated during the process of identification ( e.g. peptide counting, spectral counting), while the second makes use of extracted ion currents to quantify chromatographic peaks and infer protein abundances based on peptide quantification. These two approaches actually refer to multiple methods which have been developed during the last decade, but were submitted to deep evaluations only recently. In this paper, we compiled these different methods as exhaustively as possible. We also summarized the way they address the different problems raised by bottom-up protein quantification such as normalization, the presence of shared peptides, unequal peptide measurability and missing data. This article is part of a Special Issue entitled: Plant Proteomics— a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. [ABSTRACT FROM AUTHOR]

To create clinically useful gold nanoparticle (AuNP) based cancer therapeutics it is necessary to co-functionalize the AuNP surface with a range of moieties; e.g. Polyethylene Glycol (PEG), peptides and drugs. AuNPs can be functionalized by creating either a mixed monolayer by attaching all the moieties directly to the surface using thiol chemistry, or by binding groups to the surface by means of a bifunctional polyethylene glycol (PEG) linker. The linker methodology has the potential to enhance bioavailability and the amount of functional agent that can be attached. While there is a large body of published work using both surface arrangements independently, the impact of attachment methodology on stability, non-specific protein adsorption and cellular uptake is not well understood, with no published studies directly comparing the two most frequently employed approaches. This paper compares the two methodologies by synthesizing and characterizing PEG and Receptor Mediated Endocytosis (RME) peptide co-functionalized AuNPs prepared using both the mixed monolayer and linker approaches. Successful attachment of both PEG and RME peptide using the two methods was confirmed using Dynamic Light Scattering, Fourier Transform Infrared Spectroscopy and gel electrophoresis. It was observed that while the ‘as synthesized’ citrate capped AuNPs agglomerated under physiological salt conditions, all the mixed monolayer and PEG linker capped samples remained stable at 1 M NaCl, and were stable in PBS over extended periods. While it was noted that both functionalization methods inhibited non-specific protein attachment, the mixed monolayer samples did show some changes in gel electrophoresis migration profile after incubation with fetal calf serum. PEG renders the AuNP stable in-vivo however, studies with MDA‐MB‐231 and MCF 10A cell lines indicated that functionalization with PEG, blocks cellular uptake. It was observed that co-functionalization with RME peptide using both the mixed monolayer and PEG linker methods greatly enhanced cellular internalization compared to PEG capped AuNPs. [ABSTRACT FROM AUTHOR]

The primary functions of venoms from solitary and social wasps are different. Whereas most solitary wasps sting their prey to paralyze and preserve it, without killing, as the provisions for their progeny, social wasps usually sting to defend their colonies from vertebrate predators. Such distinctive venom properties of solitary and social wasps suggest that the main venom components are likely to be different depending on the wasps' sociality. The present paper reviews venom components and properties of the Aculeata hunting wasps, with a particular emphasis on the comparative aspects of venom compositions and properties between solitary and social wasps. Common components in both solitary and social wasp venoms include hyaluronidase, phospholipase A2, metalloendopeptidase, etc. Although it has been expected that more diverse bioactive components with the functions of prey inactivation and physiology manipulation are present in solitary wasps, available studies on venom compositions of solitary wasps are simply too scarce to generalize this notion. Nevertheless, some neurotoxic peptides (e.g., pompilidotoxin and dendrotoxin-like peptide) and proteins (e.g., insulin-like peptide binding protein) appear to be specific to solitary wasp venom. In contrast, several proteins, such as venom allergen 5 protein, venom acid phosphatase, and various phospholipases, appear to be relatively more specific to social wasp venom. Finally, putative functions of main venom components and their application are also discussed. [ABSTRACT FROM AUTHOR]

This paper presents formation of a new class of dendritic peptide nanostructures from self-assembly of diphenylalanine extracted from Alzheimer's β-amyloid polypeptide. Effects of different substrates e.g. glass, silicon and gold on morphology of dendritic nanostructures have been studied by means of AFM and FESEM. Furthermore, formation of self-assembled structures in solution has been characterized in terms of dimensions of nanotubes via Zetasizer. The results showed formation of highly ordered dendritic multi-branched structures spread on glass in which diameter of each tubular structure varies from 200 to 800 nm. Silicon substrates promoted aggregation with less dendrite characteristics. Individual nanotubes were formed on gold solid substrates. The growth of nucleation points was accelerated via spin casting. In solution, however, the diameter size showed an average of 296 nm after 1 day of self-assembly. A mechanism is proposed to explain tree-like growth of FF dendritic nanostructures. Our approach offers a biomaterial which proves highly useful for a broad range of application from drug delivery to nanofabrication techniques. [ABSTRACT FROM AUTHOR]