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An unprecedented and direct PS‐MS (paper spray ionization mass spectrometry) method was proposed for the detection of native peptides, that is, glutathiones (GSHs), homoglutathiones (hGSHs), and phytochelatins (PCs), in basil (Ocimum basilicum L.) roots before and after cadmium exposure. The roots were submitted to cold maceration followed by sonication with formic acid as the extractor solvent for sample preparation. PS‐MS was used to analyze such extracts in the positive mode, and the results allowed for the detection of several GSHs, hGSHs, and PCs. Some of these PCs were not distinguished in the control samples, that is, basil roots not exposed to cadmium. Other PCs were noticed in both types of roots, uncontaminated and cadmium‐contaminated, but the intensities were higher in the former samples. Moreover, long‐time exposure to cadmium stimulated the formation of some of these PCs and their cadmium complexes. The results, therefore, provided some crucial insights into the defense mechanism of plants against an external stress condition due to exposure to a toxic heavy metal. The present study represents a promising alternative to investigate other crucial physiological processes in plants submitted to assorted stress conditions. [ABSTRACT FROM AUTHOR]

We developed a simple, paper‐based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter‐balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes. One end of the paper strip was cut into a sharp point and positioned near the inlet of a MS. The stacked analyte bands move toward the paper tip with the EOF where they are ionized by paper spray. The device was applied to analysis of PFAS in tap water with sub part‐per‐trillion detection limits in less than ten minutes with no sample pretreatment. Analysis of opioids in urine also occurs in minutes. The crucial parameters to enable stacking, separation, and MS ionization of both positively and negatively charged analytes were determined and optimized. Experimental and computational modeling studies confirm the electrokinetic stacking and analyte transport mechanisms. On‐paper separations were carried out by stacking analyte bands at different locations depending on their electrophoretic mobility, achieving baseline separation in some cases. [ABSTRACT FROM AUTHOR]

A single amino acid in a peptide sequence can play an important role to tune the self‐assembly and hydrogelation behaviour. Here, a C‐terminal cysteine‐containing ultrashort peptide hydrogelator forms hydrogel through non‐covalent and covalent interactions. Interestingly, the hydrogel is insoluble in water and buffer solutions at different pH values (1‐13) and is thixotropic and injectable. In recent years, removing dyes from contaminated water has become a significant concern because of the shortage of freshwater resources. Therefore, the adsorption of dyes through a reliable, straightforward, nontoxic, cheap, and environmentally friendly adsorbent has become a popular topic. Hence, the hydrogelator was exploited to remove organic dyes from wastewater, harnessing its applicability in the gel phase and solid supports (filter paper and cotton). [ABSTRACT FROM AUTHOR]

Drug–drug interaction (DDI) assessments are well defined in health authority guidelines for small molecule drugs, and US Food and Drug Administration (FDA) draft guidance is now available for therapeutic proteins. However, there are currently no regulatory guidelines outlining DDI assessments for therapeutic peptides, which poses significant uncertainty and challenges during drug development for this heterogenous class of molecules. A cross‐industry peptide DDI working group consisting of experts from 10 leading companies was formed under the sponsorship of the European Federation of Pharmaceutical Industries and Associations. We aimed to capture the range of DDI studies undertaken for peptide drugs by (i) anonymously surveying relevant companies involved in peptide drug development to better understand DDI study type/timing currently performed and (ii) compiling a database containing in vitro / clinical DDI data from submission packages for recently approved peptide drugs. Our analyses highlight significant gaps and uncertainty in the field. For example, the reported timing of in vitro peptide DDI studies, if performed, vary substantially across responding companies from early research to phase III. Nearly all in vitro cytochrome P450 / transporter inhibition studies reported in the survey were negative. For the few positive hits reported, no clinical follow‐up studies were performed, questioning the clinical relevance of these findings. Furthermore, available submission packages reveal DDI likelihood is low for peptides >2 kDa, making it reasonable to adopt a risk‐based approach during drug development for larger peptides. By benchmarking the landscape of peptide DDI activities across the industry, we set the stage for future discussions with health authorities on harmonizing peptide DDI approaches. [ABSTRACT FROM AUTHOR]

A commentary of the paper 'Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology' that appeared recently in Aging Cell. The possible association of a mitochondrial haplogroup with a disease is frequently discussed. The Humanin peptide encoded by the mtDNA has been shown to play an important regulatory role in cell metabolism. There are variants of Humanin caused by different mutations and it is known that the potent form of Humanin, termed S14G, is found naturally in the people of haplogroup U6a7a1a because they have the mutation m.A2672G; however it has not been shown that having this mutation is indeed beneficial. In their paper, the authors suggest that the mitochondrial DNA mutation, m.C2639T, may be beneficial in people who are in haplogroup N1b and also carry APOE4. The mutation changes the common form of Humanin to Humanin P3S. In the study, the researchers looked at a group of Ashkenazi women who were over the age of 95, and found that a higher proportion of them carried APOE4, suggesting that Humanin P3S protected them against the adverse effects of APOE4. A study in a mouse model supported this finding by showing treatment with Humanin P3S reduced APOE4‐induced brain pathology. In the world population, there are about 500,000 Ashkenazi in haplogroup N1b, predominantly in the subgroup N1b1b1; and there are about 9.5 million non‐Ashkenazi people with the mutation m.C2639T and are therefore also in haplogroup N1b and have Humanin P3S. However, the researchers have yet to show Humanin P3S is of benefit in non‐Ashkenazi people. This paper raises the possibility of a therapeutic use of Humanin P3S in the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

This concept paper elucidates the possible influence of the electrical double layer (EDL) and the polyelectrolytic nature of bacterial cell walls on the behavior of antimicrobial peptides (AMPs) and lipopeptides. It proposes that the presence of EDL adjacent to lipid membranes may play a crucial role in inducing peptide aggregation and conformational changes, thus affecting their antimicrobial activity. Furthermore, it emphasizes that the negatively charged components in both Gram‐positive and Gram‐negative bacterial cell walls may act as polyelectrolytes, effectively reducing the critical micellization concentration (CMC) of positively charged peptides and lipopeptides. This reduction is expected to facilitate their aggregation, potentially enhancing their accumulation at the bacterial membrane and increasing their effectiveness in disrupting membrane integrity and exerting antimicrobial activity. Therefore, understanding the interplay between EDL effects, polyelectrolytic properties of bacterial cell walls, and the behavior of antimicrobial peptides is essential for elucidating their mechanisms of action and optimizing their therapeutic potential. [ABSTRACT FROM AUTHOR]

Keywords: bariatric surgery; mass spectrometry; peptide YY EN bariatric surgery mass spectrometry peptide YY 763 765 3 05/05/23 20230601 NES 230601 We note that Maurer et al., in their correspondence,[1] have raised some concerns about the preanalytical and analytical validation of the peptide YY (PYY) assay described in our paper 'The postprandial secretion of peptide YY SB 1 sb SB -36 sb and SB 3 sb SB -36 sb in obesity is differentially increased after gastric bypass versus sleeve gastrectomy'.[2] The validation and assay characteristics were not the primary objectives of the paper. We have studied the stability of both PYY species with our inhibitor mix containing DPP4 inhibitor and Aprotinin, where we spiked PYY SB 1 sb SB -36 sb and PYY SB 3 sb SB -36 sb into plasma EDTA and LH from three different volunteers. [Extracted from the article]

Cation‐π interactions, often found in protein assemblies, are characterized by favorable electrostatic interactions between an aromatic π‐electron surface and a positively charged species. There are evidences that reveal the importance of cation‐π interactions between arginine and aromatic residues in protein structure and function. In this paper, the effect of cation‐π interactions on the aggregation propensity of peptides derived from human islet polypeptide (hIAPP) was explored using UV resonance Raman and fluorescence spectroscopy. By employing an analog of hIAPP22–29 in which Phe‐23 is replaced with tryptophan (NWGAILSS), we were able to demonstrate an increase in the amyloidogenic propensity of this mutant in the presence of Zn2+ that is attributable to cation‐π interactions. In contrast, no cation‐π interactions were observed when the cationic F23R analog of hIAPP22–29 (NRGAILSS) was allowed to interact with NWGAILSS. From these observations, it was surmised that in these peptides, the dominant interaction between arginine and tryptophan involves the π‐cloud of the guanidino group and the indole ring, not cation‐π interactions. The spectroscopic data, supported by density functional theory‐based simulation results, suggest that arginine‐tryptophan interaction involves π‐π stacking where the guanidino group is oriented parallel to the indole ring. These hydrophobic interactions, coupled with the hydrotropic effect of the guanidine functionality of arginine, led to a delay in the aggregation kinetics of NWGAILSS. These unique interactions were further exploited to design a peptide inhibitor of full‐length amylin self‐assembly. [ABSTRACT FROM AUTHOR]

Tissue damage caused by an infection or an autoimmune disease triggers degradation of collagen in the extracellular matrix (ECM), which further enhances inflammation. Therefore, improving ECM in an inflamed tissue can be exploited as a potential therapeutic target. A recent study emphasised an innovative approach against COVID‐19 using polymerised type I collagen (PTIC) that improves disease severity through a hitherto unknown mechanism. In this paper, we provide an overview of potential mechanism that may explain the anti‐inflammatory effect of collagen peptides. In addition,the paper includes a brief summary of possible side effect of collagen deposition in inflammatory diseases. Altogether, current knowledge suggests that collagen may potentially reduce the residual risk in inflammatory diseases; however, the detailed mechanism remains elusive. [ABSTRACT FROM AUTHOR]

A relaxin‐like gonad‐stimulating peptide (RGP), Aso‐RGP, featuring six cysteine residues, was identified in the Crown‐of‐Thorns Starfish (COTS, Acanthaster cf. solaris) and initially produced through recombinant yeast expression. This method yielded a single‐chain peptide with an uncleaved C‐peptide (His Tag) and suboptimal purity. Our objective was to chemically synthesize Aso‐RGP in its mature form, comprising two chains (A and B) and three disulfide bridges, omitting the C‐peptide. Furthermore, we aimed to synthesize a newly identified relaxin‐like peptide, Aso‐RLP2, from COTS, which had not been previously synthesized. This paper reports the first total chemical synthesis of Aso‐RGP and Aso‐RLP2. Aso‐RGP synthesis proceeded without major issues, whereas the A‐chain of Aso‐RLP2, in its reduced and unfolded state with two free thiols, presented considerable challenges. These were initially marked by "messy" RP‐HPLC profiles, typically indicative of synthesis failure. Surprisingly, oxidizing the A‐chain significantly improved the RP‐HPLC profile, revealing the main issue was not synthesis failure but the peptide's aggregation tendency, which initially obscured analysis. This discovery highlights the critical need to account for aggregation in peptide synthesis and analysis. Ultimately, our efforts led to the successful synthesis of both peptides with purities exceeding 95 %. [ABSTRACT FROM AUTHOR]

Antibiotic‐resistant strains are an emerging threat to public health. The usage of antimicrobial peptides (AMPs) is one of the promising approaches to solve this problem. For the development of new AMPs, it is necessary to have reliable prediction methods. Recently, deep learning approaches have been used to predict AMP. In this paper, we want to compare simple and complex methods for these purposes. We used the BERT transformer to create sequence embeddings and the multilayer perceptron (MLP) and light attention (LA) approaches for classification. One of them reached about 80 % accuracy and specificity in benchmark testing, which is on par with the best available methods. For comparison, we proposed a simple method using only the amino acid composition of proteins or peptides. This method has shown good results, at the level of the best methods. We have prepared a special server for predicting the ability of AMPs by amino acid composition: http://bioproteom.protres.ru/antimicrob/. [ABSTRACT FROM AUTHOR]

INTRODUCTION: One of the main allergens in soybeans is glycinin, which seriously impacts the normal lives of allergic people. Previous studies have confirmed that thermal processing and thermal processing combined with ultrahigh‐pressure processing could significantly reduce the antigenicity of glycinin. The dominant antigen region of acidic peptide chain A2 of G2 subunit was located by phage display experiment. METHODS: In this paper, overlapping peptides and alanine substitution techniques were used to explore the key amino acids that significantly affect the antigenicity of A2 peptide chain. The purity of peptide 1, peptide 2 and peptide 3 was identified by mass spectrometry and high‐performance liquid chromatography, and the results showed that the purity of the synthesized overlapping peptide was more than 90%. SDS‐PAGE showed that the peptide was successfully coupled with bovine serum albumin. The antigenicity of the coupling peptide was tested by ELISA and Dot‐Blot, and the allergenicity was detected by reacting with the serum of patients with soybean globulin allergy. CONCLUSION: The results showed that peptide 3 has stronger antigenicity and sensitization. Alanine substitution technology allowed one to perform site‐directed mutagenesis on peptide 3. Dot‐Blot and ELISA tests showed that D259, E260, E261, Q263 and C266 may be the key amino acids that significantly affect the antigenicity of peptide 3. The research presented is of great significance for correctly guiding the production of safe food and preventing the occurrence of food allergic diseases. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Peptides have shown increasing advantages and significant clinical value in drug discovery and development. With the development of high‐throughput technologies and artificial intelligence (AI), machine learning (ML) methods for discovering new lead peptides have been expanded and incorporated into rational drug design. Predictions of peptide–protein interactions (PepPIs) and protein–protein interactions (PPIs) are both opportunities and challenges in computational biology, which will help to better understand the mechanisms of disease and provide the impetus for the discovery of lead peptides. This paper comprehensively reviews computational models for PepPI and PPI predictions. It begins with an introduction of various databases of peptide ligands and target proteins. Then it discusses data formats and feature representations for proteins and peptides. Furthermore, classical ML methods and emerging deep learning (DL) methods that can be used to train prediction models of PepPI and PPI are classified into four categories, and their advantages and disadvantages are analyzed. To assess the relative performance of different models, different validation protocols and evaluation indexes are discussed. The goal of this review is to help researchers quickly get started to develop computational frameworks using these integrated resources and eventually promote the discovery of lead peptides. [ABSTRACT FROM AUTHOR]

Summary: Nisin is a peptide with antibacterial activity against a variety of pathogens. It was originally obtained from a Lactococcus lactis. It is classified as a class I bacteriocin, as it is synthesised by ribosomes and post‐translationally modified. It has been studied extensively and has a wide range of applications in the food industry, biomedicine, veterinary, and research fields. It is approved as a food preservative by the Food and Agriculture Organization (FAO). What's more, nisin, the only antimicrobial peptide that has generally considered as safe (GRAS) status from both World Health Organization (WHO) and Food and Drug Administration (FDA), has the potential to become an important natural antibiotic as bacteria become more resistant to traditional antibiotics. However, nisin purified from biological sources usually results in low yields and high production costs, limiting industrial‐scale manufacturing and application in other fields. Hence, more methods need to be used to optimise the production of nisin. Therefore, this paper aimed to understand the structure and biosynthesis mechanism of nisin and to summarise the innovative methods for increasing the production of nisin using biosynthesis regulation. [ABSTRACT FROM AUTHOR]

Rationale: The observed isotope distribution is an important attribute for the identification of peptides and proteins in mass spectrometry-based proteomics. Sulphur atoms have a very distinctive elemental isotope definition, and therefore, the presence of sulphur atoms has a substantial effect on the isotope distribution of biomolecules. Hence, knowledge of the number of sulphur atoms can improve the identification of peptides and proteins. Methods: In this paper, we conducted a theoretical investigation on the isotope properties of sulphur-containing peptides. We proposed a gradient boosting approach to predict the number of sulphur atoms based on the aggregated isotope distribution. We compared prediction accuracy and assessed the predictive power of the features using the mass and isotope abundance information from the first three, five and eight aggregated isotope peaks. Results: Mass features alone are not sufficient to accurately predict the number of sulphur atoms. However, we reach near-perfect prediction when we include isotope abundance features. The abundance ratios of the eighth and the seventh, the fifth and the fourth, and the third and the second aggregated isotope peaks are the most important abundance features. The mass difference between the eighth, the fifth or the third aggregated isotope peaks and the monoisotopic peak are the most predictive mass features. Conclusions: Based on the validation analysis it can be concluded that the prediction of the number of sulphur atoms based on the isotope profile fails, because the isotope ratios are not measured accurately. These results indicate that it is valuable for future instrument developments to focus more on improving spectral accuracy to measure peak intensities of higher-order isotope peaks more accurately. [ABSTRACT FROM AUTHOR]

For the further study of [19F]‐alfatide, the development of highly sensitive analytical methods for its determination is an urgent issue. In this paper, a method for simultaneously determining [19F]‐alfatide and alfatide using liquid chromatography/tandem mass spectrometry was created and validated. The plasma samples were pretreated using the protein precipitation method. Poroshell 120 EC‐C18 (4.6 × 50 mm, 2.7 μm, Agilent) was used for the separation of the analytes to be measured. The mobile phase, consisting of acetonitrile and water (0.1% acetic acid, 50:50, v/v), was delivered at a flow rate of 0.60 ml/min for sample analysis. Positive electrospray ionization was performed using multiple‐reaction monitoring with transitions of m/z 715.2 → 636.6 for [19F]‐alfatide, the ion pairs 700.3 → 851.5 for alfatide and the ion pairs 237.1 → 194.2 for carbamazepine (internal standard). According to the results, the method had high specificity, precision and accuracy as well as an extended linear range. The matrix effect and extraction recovery were also acceptable. The method was successfully applied to the pharmacokinetic study of [19F]‐alfatide in rats. [ABSTRACT FROM AUTHOR]

Background: There are no diagnostic and/or prognostic markers of the treatment outcome in patients receiving allergen immunotherapy (AIT). Although numerous allergen epitopes are known, their value in this context has not been investigated. This paper deals with re‐evaluation of sera from patients who underwent AIT against rBet v 1 for treatment of their soya allergy (BASALIT trial). Objective: To evaluate the diagnostic and/or prognostic potential of allergen epitopes recognition by antibodies from patients with birch‐related soya allergy before and after rBet v 1‐immunotherapy. Methods: PR‐10 epitope‐binding profiles from 34 patients were identified in silico using a statistical peptide phage display at start and at end of AIT. IgE‐ and IgG‐binding to these peptide epitopes was measured in peptide microarrays. Clinical relevance of epitopes was evaluated by comparing these measurements to a number of treatment outcome measures recorded during double‐blind placebo‐controlled food challenge at start and end of AIT. Results: We showed that IgG‐ and IgE‐recognition of peptide epitopes after AIT were surrogate markers of 5 out of 12 analysed treatment outcome measures using this patient cohort. Seven epitopes were identified from multiple PR‐10 allergen sequences. Twenty‐six peptide epitopes were used for IgG and IgE measurements. IgE‐binding to one of the epitopes was associated with stronger intensity of oral tingling/itching after ingesting soya at start of AIT. IgG recognizing two other epitopes at start of AIT could predict decreased Cor a 1‐specific IgE concentration (p =.043) and decreased lip swelling intensity (p =.016) after AIT. Tolerance to increasing amounts of soy at food challenge correlated with IgG‐binding to another epitope at start of AIT (p =.046). Conclusion: IgG‐ and IgE‐binding to peptide epitopes in PR‐10 is a potential indicator of the outcome and clinical course of AIT of soya‐sensitized patients with rBet v 1. [ABSTRACT FROM AUTHOR]

Experimental observations have shown that peptides are chemically modified under plasma treatment, which impacts the function and lifetime of a protein. This paper investigates the interactions of reactive oxygen species (ROS) produced in atmospheric plasmas and peptides. Results show that the reactions typically start with the H abstraction from the side chain of amino acids. As the reactions continue, the introduction of O atoms is the most common reaction, and the formation of double C = C bonds, detachment of carboxyl groups, and cleavage of the ring are also observed. Moreover, the degree of oxidative modification of the peptides increases with increasing doses of ROS. This study reveals the formation and breaking of chemical bonds and the generation of new reactive groups in the structure of peptides under plasma treatment, which enables us to understand the mechanisms of plasma medicine deeply. [ABSTRACT FROM AUTHOR]

Synaptic dysfunction caused by soluble β‐amyloid peptide (Aβ) is a hallmark of early‐stage Alzheimer's disease (AD), and is tightly linked to cognitive decline. By yet unknown mechanisms, Aβ suppresses the transcriptional activity of cAMP‐responsive element‐binding protein (CREB), a master regulator of cell survival and plasticity‐related gene expression. Here, we report that Aβ elicits nucleocytoplasmic trafficking of Jacob, a protein that connects a NMDA‐receptor‐derived signalosome to CREB, in AD patient brains and mouse hippocampal neurons. Aβ‐regulated trafficking of Jacob induces transcriptional inactivation of CREB leading to impairment and loss of synapses in mouse models of AD. The small chemical compound Nitarsone selectively hinders the assembly of a Jacob/LIM‐only 4 (LMO4)/ Protein phosphatase 1 (PP1) signalosome and thereby restores CREB transcriptional activity. Nitarsone prevents impairment of synaptic plasticity as well as cognitive decline in mouse models of AD. Collectively, the data suggest targeting Jacob protein‐induced CREB shutoff as a therapeutic avenue against early synaptic dysfunction in AD. Synopsis: The synapto‐nuclear shuttling protein Jacob assembles and docks a signalosome to the transcriptional regulator CREB to promote CREB de‐phosphorylation and neuronal cell death. Here, β‐amyloid peptide (Aβ) is found to cause Alzheimer‐associated synapse loss by regulating nuclear translocation of Jacob, providing a potential target for therapeutic intervention. Aβ promotes nuclear translocation of Jacob in Alzheimer's disease (AD) patient brains and mouse hippocampal neurons.Aβ‐regulated trafficking of Jacob induces transcriptional inactivation of cAMP‐responsive element‐binding protein (CREB), leading to synapse impairment and loss in an AD mouse model.The small‐molecular compound Nitarsone selectively prevents the assembly of the Jacob/LMO4/PP1 signalosome to promote CREB transcriptional activity.Nitarsone prevents synaptic plasticity impairment and cognitive decline in mouse models of AD. [ABSTRACT FROM AUTHOR]

Peptide Science publishes peer‐reviewed papers covering all aspects of peptide synthesis, materials, structure and bioactivity. The journal includes both experimental and theoretical studies and serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. [ABSTRACT FROM AUTHOR]

Synthetic therapeutic peptides are a complex and popular class of pharmaceuticals. In recent years, peptides with proven therapeutic activity have gained significant interest in the market. The determination of synthetic peptide enantiomeric purity plays a critical role in the evaluation of the quality of the medicine. Since racemization is one of the most common side reactions occurring in AAs or peptides, enantiomeric impurities such as D‐isomers can form during the peptide synthesis or can be introduced from the starting materials (e.g., AAs). The therapeutic effect of a synthetic or semi‐synthetic bioactive peptide molecule depends on its AA enantiomeric purity and secondary/tertiary structure. Therefore, the enantiomeric purity determination for synthetic peptides is supportive for interpreting unwanted therapeutic effects and determining the quality of synthetic peptide therapeutics. However, enantiomeric purity analysis encounters formidable analytical challenges during chromatographic separation, as D/L isomers have identical physical–chemical properties except stereochemical configuration. To ensure peptides AA stereochemical configuration whether in the free or bound state, sensitive and reproducible quantitative analytical method is mandatory. In this regard, numerous analytical techniques were emerged for the quantification of D‐isomeric impurities in synthetic peptides, but still, very few reports are available in the literature. Thus, the purpose of this paper is to provide an overview of the importance, regulatory requirements, and various analytical methods used for peptide enantiomeric purity determination. In addition, we discussed the available literature in terms of enantiomeric impurity detection, common hydrolysis procedural aspects, and different analytical strategies used for sample preparation. [ABSTRACT FROM AUTHOR]

Biohybrid catalysts that operate in aqueous media are intriguing for systems chemistry. In this paper, we investigate whether control over the self‐assembly of biohybrid catalysts can tune their properties. As a model, we use the catalytic activity of functional hybrid molecules consisting of a catalytic H‐dPro‐Pro‐Glu tripeptide, derivatized with fatty acid and nucleobase moieties. This combination of simple biological components merged the catalytic properties of the peptide with the self‐assembly of the lipid, and the structural ordering of the nucleobases. The biomolecule hybrids self‐assemble in aqueous media into fibrillar assemblies and catalyze the reaction between butanal and nitrostyrene. The interactions between the nucleobases enhanced the order of the supramolecular structures and affected their catalytic activity and stereoselectivity. The results point to the significant control and ordering that nucleobases can provide in the self‐assembly of biologically inspired supramolecular catalysts. [ABSTRACT FROM AUTHOR]

Mass spectrometry is widely employed in various analytical fields for both compound identification and quantification. While in the case of compound identification, the high‐resolution instrument has increased selectivity and characterization efficiency; in the case of quantitative analysis, some critical tasks actually remain. In particular, different compounds exhibit different ionization efficiency, and this introduces the need to have a calibration standard for each analyte. In this paper, we present a new elaborative data technology, which makes it possible to standardize calibration between different instruments and molecules, making it absolute. The method was applied to data acquired by means of liquid chromatography mass spectrometry by means of an ion trap analyzer. The approach is based on the correlation of the ion trap space charge effect and the analyte concentration. The method was validated in the analysis of compounds having different polarity: hydrossitirosol, arginine, thyodiglicolic acid, and a peptide mixture of bacteria cultures derived the human gut microbiome where was found poliovirus. Moreover, it was used to obtain the absolute quantitation of peptides originating from the tryptic digestion of bacterial proteins in the fecal samples. It was therefore possible to identify and quantify different derived bacterial proteins of the poliomyelitis virus coded in bacteria derived from the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

The incidence of breast cancer has increased considerably in recent years. Many efforts have been made to develop various nano‐drug delivery systems with specific properties to achieve effective and specific therapy. The stealthy nanoliposomes are the most successful and promising candidates for providing targeted tumor therapy. In this paper, a synthesized PEtOx‐DOPE (poly(2‐Ethyl 2‐Oxazoline)‐Dioleoyl Phosphatidylethanolamine) copolymer was equipped with a breast cancer‐recognizing tumor‐homing peptide to achieve cell‐specific delivery. The prepared liposomes provided stability for 6 months, and their hydrodynamic diameters are around 100 nm. Targeted liposomes remarkably exhibited 8 times higher cellular internalization in comparison with the nontargeted cells in flow cytometry and confocal microscopy. Furthermore, liposome constructs displayed slight toxicity on HaCaT cells when treated with high doses. Hence, Peptide 18‐conjugated PEtOx‐DOPE liposome systems can serve as favorable candidates in breast cancer‐targeted therapy. [ABSTRACT FROM AUTHOR]

Spatiotemporal control for supramolecular polymerization has rendered a paradigm shift towards designing complex multi‐component supramolecular materials and derived nanocomposites. In this paper, we demonstrate self‐assembly/disassembly of amyloid‐inspired peptide nanostructures from Fmoc‐VFFAKK, 1 using gold nanoparticles (AuNPs)/cysteine mediated coupled equilibrium. We report the use of AuNPs to disaggregate the β‐sheets of the peptide nanofibers 1NF and twisted bundles 1TB to furnish dormant metastable nanoparticles. Upon cysteine mediated sequestration of the AuNPs the peptide fibers are regenerated. Such self‐assembly/disassembly of the fibers shows implication in tuning the mechanical strength of the resulting hydrogels. Further, a conformal coating of polydopamine (PDA) over the peptide fibers using the lysine amines furnishes rather robust fibers and orthogonally safeguard itself from AuNPs mediated disassembly of the fibers. Finally, such active coating with PDA having amine/quinone moieties allows selective attachment of AuNPs to furnish 1‐D organization of AuNPs over the coated peptide fibers. [ABSTRACT FROM AUTHOR]

Recent scientific evidence indicates that protein hydrolysates contain bioactive peptides that have potential benefits for human health. However, the bitter‐tasting hydrophobic peptides in protein hydrolysates negatively affect the sensory quality of resulting products and limit their utilization in food and pharmaceutical industries. The approaches to reduce, mask, and remove bitter taste from protein hydrolysates have been extensively reported. This review paper focuses on the advances in the knowledge regarding the structure–bitterness relationship of peptides, the release mechanism of bitter peptides, and the debittering methods for protein hydrolysates. Bitter tastes generating with enzymatic hydrolysis of protein is influenced by the type, concentration, and bitter taste threshold of bitterness peptides. A "bell‐shaped curve" is used to describe the relationship between the bitterness intensity of the hydrolysates and the degree of hydrolysis. The bitter receptor perceives bitter potencies of bitter peptides by the hydrophobicity recognition zone. The intensity of bitterness is influenced by hydrophobic and electronic properties of amino acids and the critical spatial structure of peptides. Compared to physicochemical debittering (i.e., selective separation, masking of bitter taste, encapsulation, Maillard reaction, and encapsulation) and other biological debittering (i.e., enzymatic hydrolysis, enzymatic deamidation, plastein reaction), enzymatic hydrolysis is a promising debittering approach as it combines protein hydrolyzation and debittering into a one‐step process, but more work should be done to advance the knowledge on debittering mechanism of enzymatic hydrolysis and screening of suitable proteases. Further study can focus on combining physicochemical and biological approaches to achieve high debittering efficiency and produce high‐quality products. [ABSTRACT FROM AUTHOR]

Background: ω‐hexatoxin‐Hvn1b is an insecticidal toxin produced by the Tasmanian funnel‐web spider (Hadronyche venenata), that can be exploited for development of novel bioinsecticides. Due to its larger size and low membrane permeability, this toxin usually has a slower mode of action compared to conventional small molecule insecticides. Nanoscale materials have unique optical, electrical, mechanical and biological properties, and show great application prospects for pesticide delivery. Results: The physical and chemical properties of nanocapsules were characterized using transmission electron microscopy, laser particle size analysis, Fourier transform infrared spectroscopy, contact angle testing and with a fluorescence spectrophotometer. The results indicated that the nanocapsules were spherical, with an average particle size of 197.70 nm, the encapsulation efficiency rate was 75.82% and the Zeta potential was −32.90 mV. Penetration experiments showed that the nanocapsules could promote protein passage through the intestinal tract of Spodoptera litura and reach the body fluid. Then we expressed ω‐hexatoxin‐Hvn1b by prokaryotic expression. Bioassay results showed that the oral toxicity of ω‐hexatoxin‐Hvn1b nanocapsules to S. litura was higher than that of the ω‐hexatoxin‐Hvn1b. Conclusion: In this paper, we reported a construction method of spider venom peptide nanocapsules based on polylactic‐co‐glycolic acid by multiple emulsion for delivery of protein to improve the insecticidal effect and oral activity of ω‐hexatoxin‐Hv1a. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) arises when cells are under stress, and their membranes are damaged. They release damage‐associated molecular patterns (DAMPs) that stimulate and drive the type and magnitude of the immune response. In the presence of an antigen, DAMPs ride the longevity and efficacy of antigen‐specific immunity. Yet, no tool can induce the controlled ICD with predictable results. A peptide‐based tool, [II], is designed that aggregates in the cell and causes cell membrane damage, generates ICD and DAMPs release on various cell types, and hence can act as an adjuvant. An influenza vaccine is prepared by combining [II] with influenza hemagglutinin (HA) subunit antigens. The results show that [II] induced significantly higher HA‐specific immunoglobulin G1 (IgG1) and IgG2a antibodies than HA‐only immunized mice, while the peptide itself did not elicit antibodies. This paper demonstrates the first peptide‐aggregation induced immunogenic rupture (PAIIR) approach as a vaccine adjuvant. PAIIR is a promising adjuvant with a high potential to promote universal protection upon influenza HA vaccination. [ABSTRACT FROM AUTHOR]

CD247, which is also known as CD3ζ, CD3H, CD3Q, CD3Z, IMD25, T3Z and TCRZ, encodes CD3ζ protein, which is expressed primarily in natural killer (NK) and T cells. Since the discovery of the ζ peptide in 1986, it has been continuously investigated. In this paper, we review the composition, molecular mechanisms and regulatory factors of CD247 expression in T cells; and review the autoimmune diseases, tumours and inflammatory diseases associated with CD247, providing a detailed and comprehensive reference for further research on the mechanism of CD247 and related diseases. [ABSTRACT FROM AUTHOR]

Medium sized molecules such as peptides and macrocycles have recently drawn much attention as potent sources of medicinal lead compounds, whereas the possibility of obtaining a practical drug from them remains limited. The present paper describes a concept of discovering novel medicinal targets or binding modes as well as lead compounds by the one‐peptide‐on‐one‐bead (OPOB) technology for comprehensive screening. The difficulty and problems in conventional drug discovery methods that generally deal with one predetermined target are considered. The building blocks used for the present libraries were selected based on previous results in development of peptidic drugs. Each constituent has the common structure of cyclic form prepared by disulfide of cysteinyl residues or thioether linkages, additionally a methionine residue was inserted for the site‐specific rapid cleavage by cyanogen bromide to liberate the immobilized peptides allowing reliable characterization by MALDI‐TOF‐MS/MS without LC‐purification. Thus, a high throughput construction method for cyclic peptide libraries as well as characterization of single bead are proposed for drug discovery. [ABSTRACT FROM AUTHOR]

The development of peptidomimetics to modulate the conformational profile of peptides has been extensively studied in the fields of biological and medicinal chemistry. However, large‐scale synthesis of peptidomimetics with both an ordered sequence and a controlled secondary structure is highly challenging. In this paper, the framework of peptidomimetics has been designed to be alternating an achiral α,α‐disubstituted α‐amino acid unit and a chiral α‐methylphenylalanine unit. The polymers are synthesized via invented Ugi reaction‐based polycondensation technique. The chiral higher‐order structures of the alternating peptides are evaluated mainly through circular dichroism (CD) spectroscopy. The UV–Vis and CD spectra of the polymers in three solvents are systematically measured at various temperatures. The anisotropic factors of CD (gCD) values are calculated to know the chiroptical response. The results indicate the characteristic conformational behaviors. In a polar solvent, the hydrogen bonds between the N‐H group of MePhe unit and the C=O of α,α‐diphenylglycine unit outweigh the intraresidue hydrogen bonds in α,α‐diphenylglycine unit, leading to the formation of a prevailing preferred‐handed 310‐helical conformation. On the other hand, in a less polar solvent, the intrachain hydrogen bonds switch to intraresidue hydrogen bonds in α,α‐diphenylglycine unit, which make the polymer adopting a prevailing extended planar C5‐conformation. [ABSTRACT FROM AUTHOR]

Since the global peptide drug market demand has been predicted to increase, highly efficient and inexpensive mass scale peptides are required. However, the production process raises questions about the cost of energy input, scale‐up production, raw materials, and solvents treatment. This paper introduces 2 methods for the 2–4 mer oligopeptides bond formation for batch reaction utilizing 50–100 mol% of a mild Brønsted acid under the mild condition. One of the methods has been capably adapted to flow synthesis at room temperature using organic solvents with boiling points below 100 °C. The method applies the tert‐butoxycarbonyl amino methoxy group, forming the desired dipeptide without solvent at mild temperatures. Furthermore, the conversion of the carboxylic acid leaving the group to phenyl ester promotes peptide bond formation, and the reaction were applied to di, tri, and tetrapeptide bond formation in excellent yield without notable racemization at ambient temperature (up to >99 % yield and 99 : 1 dr). Finally, this study proposes this new production method to overcome the limited scale‐up production by reaction device scale: liquid phase biomimetic catalytic peptide flow synthesis utilizing a mild Brønsted acid. [ABSTRACT FROM AUTHOR]

Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have become agents of choice for people with type 2 diabetes (T2D) with established cardiovascular disease or in high‐risk individuals. With currently available GLP‐1 RAs, 51%‐79% of subjects achieve an HbA1c target of less than 7.0% and 4%‐27% lose 10% of body weight, illustrating the need for more potent agents. Three databases (PubMed, Cochrane, Web of Science) were searched using the MESH terms 'glucagon‐like peptide‐1 receptor agonist', 'glucagon receptor agonist', 'glucose‐dependent insulinotropic peptide', 'dual or co‐agonist', and 'tirzepatide'. Quality of papers was scored using PRISMA guidelines. Risk of bias was evaluated using the Cochrane assessment tool. An HbA1c target of less than 7.0% was attained by up to 80% with high‐dose GLP‐1 RAs and up to 97% with tirzepatide, with even up to 62% of people with T2D reaching an HbA1c of less than 5.7%. A body weight loss of 10% or greater was obtained by up to 50% and up to 69% with high‐dose GLP‐1 RAs or tirzepatide, respectively. The glucose‐ and weight‐lowering effects of the GLP‐1/glucagon RA cotadutide equal those of liraglutide 1.8 mg. Gastrointestinal side effects of high‐dose GLP‐1 RAs and co‐agonists occurred in 30%‐70% of patients, mostly arising within the first 2 weeks of the first dose, being mild or moderate in severity, and transient. The development of high‐dose GLP‐1 RAs and the dual GLP‐1/glucose‐dependent insulinotropic peptide RA tirzepatide resulted in increasing numbers of people reaching HbA1c and body weight targets, with up to 62% attaining normoglycaemia with 15‐mg tirzepatide. Whether this will also translate to better cardiovascular outcomes and affect treatment guidelines remains to be studied. [ABSTRACT FROM AUTHOR]

Electrically controllable deoxyribonuclic acid (DNA) nanolevers are used to investigate the binding interaction between Influenza A/Aichi/2/1968 and the peptide called "PeB", which specifically binds the viral surface protein hemagglutinin. PeB is immobilized on gold electrodes of a "switchSENSE" biochip by conjugation to DNA‐strands that are hybridized to complementary anchors. The surface‐tethered DNA strand carries a fluorophore while the complementary strand is a multivalent arrangement carrying up to three PeB peptides. The nanolevers are kept upright (static) by applying a negative potential. Signal read‐out for this static measurement mode is the change in fluorescence intensity due to changes in the local environment of the dye upon binding. Measurements of virus‐peptide interaction show that the virus material specifically binds to the immobilized peptides and remains bound throughout the measurement time. Immobilized viruses are subsequently used as ligands to characterize oligovalent peptide binding to hemagglutinin, revealing rate constants of the interaction. Moreover, three Influenza A subtypes are compared in their binding behavior. Overall, this paper shows the ability to immobilize virus material on a sensor surface, which allows to target virus‐proteins in their native environment. The "switchSENSE" method is therefore applicable to characterize virus‐receptor interactions. [ABSTRACT FROM AUTHOR]

The interactions between ligands and polymers are of great interest to drug delivery researches. In this work for the first time, Poly (lactic‐co‐glycolic acid) based polymers with arginine‐glycine‐aspartate (RGD) peptide ligands which are immediately self‐assembled into micellar nanoparticles (NPs) in contact with water have been investigated in the atomistic level. In this regard, the effect of polymer and RGD concentrations on the stability, size, interaction energies and other molecular properties of nanocarriers has been investigated using molecular dynamics simulation. In the next step, the microfluidic micellization and docetaxel (DTX) encapsulation has been simulated in comparison to bulk micellization. Results indicated that by employing only 20 wt % RGD‐conjugated polymer, the particles reach the stable properties and compactness without DTX. But, when the DTX was added, 30 wt.% of RGD‐conjugated polymers that assembled in microfluidic system is the best state nanocarrier for the smart target drug delivery for transfer of DTX drug into the Cancer cell. Comparisons of the results acquired in the current paper confirmed that engineering and tuning the self‐assembly in the interface of phases in microchennel resulted in a precise control on the particle size and resulted in the preparation of smaller and more stable NPs that can be exploited as ultra‐small, smart drug carriers. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are a significant and growing burden on global health services, and it is now accepted that impairment of vascular function represents a major preliminary step in the development of CVD. There is considerable interest in identifying both causal factors of impaired vascular function, as well as related nutritional factors that may lower the risk of developing CVD, and food‐derived bioactive peptides and amino acids have emerged as one such area. Dairy foods contain two groups of proteins, whey proteins and caseins, which represent a rich source of bioactive peptides that are released during food processing and/or digestion. These peptides have a number of physiological activities including the potential to reduce blood pressure. Research, including acute and longer‐term randomised controlled trials, animal models and in vitro models has demonstrated the potential impact of dairy proteins on vascular function. The purpose of this paper is to narratively review the evidence, primarily from randomised controlled trials, examining the effects of whey proteins, their peptides and amino acids on vascular function and related issues including blood pressure. In addition, it will explore the potential underlying mechanisms responsible for these effects. It concludes that there is increasing evidence that whey proteins, and notably the bioactive peptides and amino acids released during their digestion, can have beneficial effects on aspects of vascular function and thus contribute to CVD risk reduction. It also highlights a number of beneficial effects of whey proteins including those on blood pressure, arterial stiffness, nitric oxide production and inflammation. [ABSTRACT FROM AUTHOR]

Introduction: The MHC‐peptide interaction has a subtle influence on host resistance to virus. This paper aims to study the relationship between MHC‐peptide interaction and MHC‐related virus‐resistance. Methods: By 3D homology modeling, the structure of chicken BF2 molecule BF2*0201 (PDB code: 4d0d) was studied and compared with the known structures of BF2 molecule BF2*0401 (PDB code: 4e0r) to elucidate the characteristics of BF2*0201‐binding antigenic peptides. Results: The results show that due to the amino acid difference between the two binding groove of 4e0r and 4d0d, the size of the binding groove of the two are 1130 ų and1380 ų respectively, indicating the amino acid species that 4e0r binding peptide has lower selectivity than 4d0d; and because of large side chain conformation of Arg (especially Arg111) of 4e0r replaced by small side chain Tyr111 of 4d0d, the volume of central part of the binding groove of 4d0d is obviously larger than that of 4e0r, indicating that the restrictive of binding antigenic peptides for 4d0d is narrower than that of 4e0r; and on account of the chargeability of the binding groove of the two are different, namely the binding groove chargeability of 4e0r (strong positive polarity) and 4d0d (weak negative polarity). Conclusion: There are generally more peptides presented by the BF2 of B2 haplotype than by that of B4 haplotype, leading to more resistance of B2 than that of B4 to virus. [ABSTRACT FROM AUTHOR]

This paper describes a method that combines a microfluidic device and self‐assembled monolayers for matrix‐assisted laser desorption/ionization mass spectrometry (SAMDI) mass spectrometry to calculate the cooperativity in binding of calcium ions to peptidylarginine deiminase type 2 (PAD2). This example uses only 120 μL of enzyme solution and three fluidic inputs. This microfluidic device incorporates a self‐assembled monolayer that is functionalized with a peptide substrate for PAD2. The enzyme and different concentrations of calcium ions are flowed through each of eight channels, where the position along the channel corresponds to reaction time and position across the channel corresponds to the concentration of Ca2+. Imaging SAMDI (iSAMDI) is then used to determine the yield for the enzyme reaction at each 200 μm pixel on the monolayer, providing a time course for the reactions. Analysis of the peptide conversion as a function of position and time gives the degree of cooperativity (n) and the concentration of ligand required for half maximal activity (K0.5) for the Ca2+ – dependent activation of PAD2. This work establishes a high‐throughput and label‐free method for studying enzyme‐ligand binding interactions and widens the applicability of microfluidics and matrix‐assisted laser desorption/ionization mass spectrometry (MALDI) imaging mass spectrometry. [ABSTRACT FROM AUTHOR]

Recently, we presented a strategy for packaging peptides as side‐chains in high‐density brush polymers. For this globular protein‐like polymer (PLP) formulation, therapeutic peptides were shown to resist proteolytic degradation, enter cells efficiently and maintain biological function. In this paper, we establish the role charge plays in dictating the cellular uptake of these peptide formulations, finding that peptides with a net positive charge will enter cells when polymerized, while those formed from anionic or neutral peptides remain outside of cells. Given these findings, we explored whether cellular uptake could be selectively induced by a stimulus. In our design, a cationic peptide is appended to a sequence of charge‐neutralizing anionic amino acids through stimuli‐responsive cleavable linkers. As a proof‐of‐concept study, we tested this strategy with two different classes of stimuli, exogenous UV light and an enzyme (a matrix metalloproteinase) associated with the inflammatory response. The key finding is that these materials enter cells only when acted upon by the stimulus. This approach makes it possible to achieve delivery of the polymers, therapeutic peptides or an appended cargo into cells in response to an appropriate stimulus. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are an ancient and innate system of host defence against a wide range of microbial assailants. Mechanistically, unstructured peptides undergo a secondary structure transition into amphipathic α‐helices, upon contact with membrane surfaces. This leads to peptide binding and removal of the membrane components in a detergent‐like manner or via self‐organisation into trans‐membrane pores (either barrel‐stave or toroidal pore) thereby destroying the microbe. Self‐assembly of antimicrobial peptides into oligomers and ultimately amyloid has been mostly examined in parallel, however recent findings link diseases, such as Alzheimer's disease as an aberrant activity of a protective neuropeptide with antimicrobial activity. These self‐assembled oligomers can also interact with membranes. Here, we review those antimicrobial peptides reported to self‐assemble into amyloid, where supported by structural evidence. We consider their membrane activities as antimicrobial peptides and present evidence of consistent self‐assembly patterns across major evolutionary groups. Trends are apparent across these groups, supporting the mounting data that self‐assembly of antimicrobial peptides into amyloid should be considered as synergistic to the antimicrobial peptide response. [ABSTRACT FROM AUTHOR]

Summary: The aim of the present study was to investigate the effect of peptides derived from Colla corii asini on tyrosinase. The sequences of Colla corii asini–derived peptides were identified using mass spectrometry. To characterise the potential peptides with tyrosinase inhibitory activity and clarify their molecular mechanism, both in silico digestion and molecular docking were used. In addition, the tyrosinase inhibitory activities of potential peptides in vitro were also validated. The results showed that Colla corii asini consisted of 472 peptides, and most peptides derived from collagen. Peptides DGGR, DGD, NAGE, LVGE and GSEG were released from the digestion of Colla corii asini‐derived peptides and possessed potent inhibitory activity against tyrosinase with IC50 values of 0.92, 0.50, 0.77, 0.66 and 0.69 mg mL−1, respectively. The molecular interaction results showed that hydrogen bond and van der Waals interactions are important forces in the interaction of peptides with tyrosinase. Surface forces containing aromatic interaction, hydrogen bond, hydrophilicity and solvent‐accessible surface contributed to the interaction between tyrosinase and peptides. [ABSTRACT FROM AUTHOR]

Peptide Science publishes peer‐reviewed papers covering all aspects of peptide synthesis, materials, structure and bioactivity. The journal includes both experimental and theoretical studies and serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. [ABSTRACT FROM AUTHOR]

Anti‐cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin‐I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin‐I, which can self‐assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia. Mechanistically, Lycosin‐I selectively binds to the K562 cell membrane, likely due to its preferential interaction with negatively charged phosphatidylserine, and rapidly triggers membrane lysis, particularly at high concentrations. In addition, Lycosin‐I induces apoptosis, cell cycle arrest in the G1 phase and ferroptosis in K562 cells by suppressing the PI3K‐AKT‐mTOR signaling pathway and activating cell autophagy at low concentrations. Furthermore, intraperitoneal injection of Lycosin‐I inhibits tumor growth of K562 cells in a nude mouse xenograft model without causing side effects. Collectively, the multimodal effect of Lycosin‐I can provide new insights into the mechanism of ACPs, and Lycosin‐I, which is characterized by high potency and specificity, can be a promising lead for the development of anti‐leukemia drugs. [ABSTRACT FROM AUTHOR]

The first systematic reviews of the effects of exercise on appetite‐regulation and energy intake demonstrated changes in appetite‐regulating hormones consistent with appetite suppression and decreases in subsequent relative energy intake over a decade ago. More recently, an intensity‐dependent effect and several potential mechanisms were proposed, and this review aims to highlight advances in this field. While exercise‐induced appetite suppression clearly involves acylated ghrelin, glucagon‐like peptide‐1 may also be involved, though recent evidence suggests peptide tyrosine tyrosine may not be relevant. Changes in subjective appetite perceptions and energy intake continue to be equivocal, though these results are likely due to small sample sizes and methodological inconsistencies. Of the proposed mechanisms responsible for exercise‐induced appetite suppression, lactate has garnered the most support through in vitro and in vivo rodent studies as well as a growing amount of work in humans. Other potential modulators of exercise‐induced appetite suppression may include sex hormones, growth‐differentiation factor 15, Lac‐Phe, brain‐derived neurotrophic factor, and asprosin. Research should focus on the mechanisms responsible for the changes and consider these other modulators (i.e., myokines/exerkines) of appetite to improve our understanding of the role of exercise on appetite regulation. [ABSTRACT FROM AUTHOR]

To ensure compositional consistency while mitigating potential immunogenicity for stem cell therapy, synthetic scaffolds have emerged as compelling alternatives to native extracellular matrix (ECM). Substantial progress has been made in emulating specific natural traits featuring consistent chemical compositions and physical structures. However, recapitulating the dynamic responsiveness of the native ECM involving chemical transitions and physical remodeling during differentiation, remains a challenging endeavor. Here, the creation of adaptive scaffolds is demonstrated through sequential protein‐instructed molecular assembly, utilizing stage‐specific proteins, and incorporating in situ assembly technique. The procedure is commenced by introducing a dual‐targeting peptide at the onset of stem cell differentiation. In response to highly expressed integrins and heparan sulfate proteoglycans (HSPGs) on human mesenchymal stem cell (hMSC), the peptides assembled in situ, creating customized extracellular scaffolds that adhered to hMSCs promoting osteoblast differentiation. As the expression of alkaline phosphatase (ALP) and collagen (COL‐1) increased in osteoblasts, an additional peptide is introduced that interacts with ALP, initiating peptide assembly and facilitating calcium phosphate (CaP) deposition. The growth and entanglement of peptide assemblies with collagen fibers efficiently incorporated CaP into the network resulting in an adaptive biphasic scaffold that enhanced healing of bone injuries. [ABSTRACT FROM AUTHOR]

Constructing artificial ion channels is a challenging task. Herein, the de novo design of transmembrane ion channels made up of amphiphilic peptide–oligourea chimeric helices is described. They consist of an oligourea segment (7‐mer) attached to the C‐terminus of a short peptide (8‐mer). Mass spectrometry (MS) and transmission electron microscopy (TEM) analyses show that in an aqueous solution, two of these chimeras (HPU‐E and HPU‐N) independently form defined oligomeric structures. TEM also shows that they form fiber bundles. The third related chimera HPU‐F does not oligomerize (MS) but forms spherical nanostructures (TEM). HPU‐E and HPU‐N exhibit anion transport activity across lipid bilayers via antiport mechanism (HPU‐N > HPU‐E). The anion selectivity of HPU‐N is Cl−>NO3− > Br−>SCN− > I− > AcO−>F−, which can be due to anion binding within the channels rather than size exclusion. Patch‐clamp data support HPU‐N's Cl− selectivity (PCl−/PI− = 3.26). X‐ray crystal structure (1.77 Å) of HPU‐N reveals well‐packed α‐helices, and cryo‐electron microscopy data shows the formation of nanotubes (13.7 Å diameter pores) and transmembrane channels. The study shows that α‐peptide–oligourea‐based de novo design can yield unique bioactive molecules with defined structures and functions. [ABSTRACT FROM AUTHOR]

The silicifying peptide R5 (H‐SSKKSGSYSGSKGSKRRIL‐OH) derived from diatoms is extensively investigated, but the mechanism underlying silica synthesis by R5 or R5‐alike peptides is still poorly understood, limiting the design of silicifying peptides Herein, machine learning techniques are used to design peptides with silicifying functionality. Utilizing a comprehensive dataset of peptides and their corresponding silicification outcomes, a deep learning model based on antimicrobial peptide migration learning is created. This model exhibits the remarkable capability to accurately predict peptide sequences with a high potential for facilitating silica formation. A selection of artificially designed peptides can catalyze the biomimetic synthesis of nanosilica, some of which demonstrate better catalytic activity with a wider pH range and faster reaction rate compared with the peptide R5. Additionally, the designed peptide is used to wrap the model diatom Phaeodactylum tricornutum with nanosilica coatings, resulting in a significant enhancement in the UV resistance of cells. The new silicified peptides are highly significant for advancing the understanding of the silica synthesis mechanism in diatoms, and the encapsulation of P. tricornutum has potential benefits in the development of new biosensors. [ABSTRACT FROM AUTHOR]

DNA damage plays a significant role in the tumorigenesis and progression of the disease. Abnormal DNA repair affects the therapy and prognosis of cancer. In this study, it is demonstrated that the deubiquitinase USP25 promotes non‐homologous end joining (NHEJ), which in turn contributes to chemoresistance in cancer. It is shown that USP25 deubiquitinates SHLD2 at the K64 site, which enhances its binding with REV7 and promotes NHEJ. Furthermore, USP25 deficiency impairs NHEJ‐mediated DNA repair and reduces class switch recombination (CSR) in USP25‐deficient mice. USP25 is overexpressed in a subset of colon cancers. Depletion of USP25 sensitizes colon cancer cells to IR, 5‐Fu, and cisplatin. TRIM25 is also identified, an E3 ligase, as the enzyme responsible for degrading USP25. Downregulation of TRIM25 leads to an increase in USP25 levels, which in turn induces chemoresistance in colon cancer cells. Finally, a peptide that disrupts the USP25‐SHLD2 interaction is successfully identified, impairing NHEJ and increasing sensitivity to chemotherapy in PDX model. Overall, these findings reveal USP25 as a critical effector of SHLD2 in regulating the NHEJ repair pathway and suggest its potential as a therapeutic target for cancer therapy. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease, with limited therapeutic options available. Impaired autophagy resulting from aberrant TRB3/p62 protein‐protein interactions (PPIs) contributes to the progression of IPF. Restoration of autophagy by modulating the TRB3/p62 PPIs has rarely been reported for the treatment of IPF. Herein, peptide nanofibers are developed that specifically bind to TRB3 protein and explored their potential as a therapeutic approach for IPF. By conjugating with the self‐assembling fragment (Ac‐GFFY), a TRB3‐binding peptide motif A2 allows for the formation of nanofibers with a stable α‐helix secondary structure. The resulting peptide (Ac‐GFFY‐A2) nanofibers exhibit specific high‐affinity binding to TRB3 protein in saline buffer and better capacity of cellular uptake to A2 peptide. Furthermore, the TRB3‐targeting peptide nanofibers efficiently interfere with the aberrant TRB3/p62 PPIs in activated fibroblasts and fibrotic lung tissue of mice, thereby restoring autophagy dysfunction. The TRB3‐targeting peptide nanofibers inhibit myofibroblast differentiation, collagen production, and fibroblast migration in vitro is demonstrated, as well as bleomycin‐induced pulmonary fibrosis in vivo. This study provides a supramolecular method to modulate PPIs and highlights a promising strategy for treating IPF diseases by restoring autophagy. [ABSTRACT FROM AUTHOR]

Myocardial ischemia‐reperfusion injury (MIRI) represents a critical pathology in acute myocardial infarction (AMI), which is characterized by high mortality and morbidity. Cardiac microvascular dysfunction contributes to MIRI, potentially culminating in heart failure (HF). Pigment epithelium‐derived factor (PEDF), which belongs to the non‐inhibitory serpin family, exhibits several physiological effects, including anti‐angiogenesis, anti‐inflammatory and antioxidant properties. Our study aims to explore the impact of PEDF and its functional peptide 34‐mer on both cardiac microvascular perfusion in MIRI rats and human cardiac microvascular endothelial cells (HCMECs) injury under hypoxia reoxygenation (HR). It has been shown that MIRI is accompanied by ferroptosis in HCMECs. Furthermore, we investigated the effect of PEDF and its 34‐mer, particularly regarding the Nrf2/HO‐1 signalling pathway. Our results demonstrated that PEDF 34‐mer significantly ameliorated cardiac microvascular dysfunction following MIRI. Additionally, they exhibited a notable suppression of ferroptosis in HCMECs, and these effects were mediated through activation of Nrf2/HO‐1 signalling. These findings highlight the therapeutic potential of PEDF and 34‐mer in alleviating microvascular dysfunction and MIRI. By enhancing cardiac microvascular perfusion and mitigating endothelial ferroptosis, PEDF and its derivative peptide represent promising candidates for the treatment of AMI. [ABSTRACT FROM AUTHOR]