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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]

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]

Phage display biopanning is used to identify peptides that show material-selective adsorption, effectively distinguishing between the cellulose of paper and the printed toner of standard office laser printers. These genetically selected 12mer peptides can selectively coat either non-printed cellulose or printed toner patterns. Furthermore, triazolindione ligation chemistry is exploited to introduce, for example, dyes or functional peptides selectively to the coatings. The strategy offers an easy access towards the patterned functionalization of paper-based materials, which potentially is of relevance for low-cost diagnostics or biomedical devices. [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]

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]

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]

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]

The article discusses the use of diagnostic biomarkers for prediction of adverse early pregnancy outcomes. Topics mentioned include the use of a biomarker for reduction of clinical burden of pregnancy of unknown location cases, the controversies surrounding the use of biomarkers, such as human chorionic gonadotrophin and progesterone, and the categorization of biomarkers in early pregnancy based on their biological origin.

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Purpose: The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both 68Ga‐DOTA peptides and 18F‐fluorodihydroxyphenyl‐ l‐alanine (18F‐DOPA) PET/computed tomography (CT). As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta‐analysis to assess the available data. Methods: PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of 68Ga‐DOTA peptides and 18F‐DOPA PET/CT; papers up to February 2021 were considered. In each study, we considered sensitivity in terms of patient‐based analysis (PBA), region‐based analysis (RBA) and lesion‐based analysis (LBA), and pooled the results yielded by each tracer. Multidisciplinary follow‐up served as the standard of truth. Results: Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NETs patients were included. The pooled sensitivity of 18F‐DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. 68Ga‐DOTA peptides PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of 18F‐DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of 18F‐DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild‐to‐high heterogeneity was found; however, no publication bias was observed. Conclusion: Both 18F‐DOPA PET/CT and 68Ga‐DOTA‐peptides PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non‐negligible difference in favour of 18F‐DOPA PET/CT was observed. Thus, the use of 18F‐DOPA PET/CT could be considered as a first‐line molecular procedure in intestinal NETs. [ABSTRACT FROM AUTHOR]

Milk proteins are recognized as the main source of biologically active peptides. Casein's primary structure contains several bioactive amino acid sequences on its latent inactive form. These potential active sequences can be released during cheese manufacture and ripening, giving rise to peptides with biological activity such as antihypertensive, antidiabetic, antioxidant, immunomodulatory, and mineral‐binding properties. However, the presence of biopeptides in cheese does not imply actual biological activity in vivo because these peptides can be further hydrolyzed during gastrointestinal transit. This paper reviews the recent advances in biopeptide formation in ripened cheeses production, focusing on the influence of technological parameters affecting proteolysis and the consequent release of peptides. The main discoveries in the field of cheese peptide digestion through recent in vivo and in vitro model studies are also reviewed. © 2021 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background: To assess the relationship of chosen salivary proteins and peptides levels with the occurrence of caries in children. Methods: PubMed, MEDLINE and EMBASE databases from 2000 to 2018 were researched for original observational studies published in English. The risk of bias and quality of the included papers were assessed regarding the guidelines by Fowkes and Fulton. Results: Twenty‐two studies were included in the review, from which the issue of glycoproteins (including immunoglobulins), AMPs and salivary enzymes was discussed. The research involved primary dentition (13 papers), as well as mixed (7) and permanent dentition (5). Caries assessment included visual inspection, dmft/s and DMFT/S indexed; quantity of Streptococcus mutans and Lactobacillus spp. bacteria; and caries risk assessment. Discussion: The results of studies regarding the connection between salivary peptides and proteins and caries development in children are promising; however, further investigations should be undertaken. The majority of studies included are case–control and cross‐sectional; however, it is necessary to conduct more cohort studies with adequate follow‐up prior to considering this as markers for caries risk assessment. [ABSTRACT FROM AUTHOR]

The alteration of amino acid register in peptides could affect their folding properties and thus functions. The effect of sequence in metal ion induced folding of peptide/protein is important in the design of new functional protein structures, such as biomimetics. In this paper, a set of hairpin peptides with identical composition but different histidine locations have been designed to exploit the metal ion‐mediated peptide intramolecular folding transformation through the adjustment of histidine and lysine residue locations. The results demonstrated that the histidine positions in peptide sequence could dramatically affect the coordination modes between peptides and Cu(II) ion. The Cu(II) coordination could affect the secondary structure transformation and self‐assembly along with electrostatic interaction and hydrogen bonding synergistically. Three molecules with VHVH sequence at each side of the turn segment (VDPPT) were apt to coordinate with Cu(II) ion with three or four histidines. The closer the VHVH motifs were to the turn segment, the more easier the molecules were to form β sheet structure with the promotion of Cu(II) ions. These results demonstrated that the purposeful location of key amino acids in peptides could achieve the controllable conformation transformation of hairpin peptides, which provides useful strategies for biomimetic design, such as metalloenzymes. [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]

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]

Summary: This paper investigated umami hexapeptides derived from myosin of Atlantic cod (Gadus morhua) using homology modelling, molecular docking, taste evaluation and e‐tongue verification. After hydrolysing and prediction in silico, potential bioactivity, toxicity and physicochemical properties of 48 hexapeptides were predicted. Five hexapeptides were selected to dock with the T1R1–T1R3 homology model which was built with SWISS‐MODEL. Docking results showed that the five hexapeptides could enter the docking region, and INKPGL, SDSCIR and GPDPER had the lowest CDOKER_ENERGY. E‐tongue result showed that the umami and richness value of all the three hexapeptides in 0.4 mg mL−1 were higher than a 0.1% MSG solution. Sensory evaluation result showed that INKPEL had the strongest umami taste among the three hexapeptides and the umami threshold value was 0.25 mg mL−1. These results suggested that homology modelling can be used for predicting umami peptides, and three umami hexapeptides were identified by in silico screening. [ABSTRACT FROM AUTHOR]

In this research, we focus on enzymatic hydrolysis of chicken feathers, after chemical or chemical and ultrasound pretreatment. Our result illustrated that ultrasound pretreatment preserved the main structure and amino acid composition of extracted keratin as confirmed by the Fourier‐transform infrared (FTIR) spectroscopy and gel‐electrophoresis analysis. In addition, investigation showed that ultrasound‐assisted chemical treatment was more effective on enzymatic hydrolysis and bioactivity as compared to only the chemical treatment. Thermo gravimetric analysis (TGA) characterization of hydrolyzed products, using Alcalase enzyme at different times, showed that decomposition temperature was decreased during enzymatic hydrolysis and the best antioxidant activity was achieved after 30 min of hydrolysis with the value of 90.43±4.03 % (5 mg/ml concentration). Also, it was found that hydrolyzed product indicated no cytotoxicity to SK‐N‐MC cells when the concentration is less than 0.312 mg/ml. In this paper, the results demonstrated that the ultrasonic‐assisted enzymolysis processing seems to be effective for producing keratin antioxidant hydrolysate. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness and safety of erenumab in patients with chronic migraine in the real‐world setting of 3 headache centers in Australia. Methods: Patients with migraine were prescribed erenumab (70 or 140 mg) in the setting of either a product familiarization program or paid access to the medication in 3 headache centers in Australia. We obtained baseline and monthly prospective data on monthly headache days, monthly migraine days, monthly triptan use days, monthly codeine use days, Headache Impact Test‐6 scores, and adverse reactions. In this paper, we present our data at 3 and 6 months in our subgroup of patients with chronic migraine with and without medication overuse. Results: A total of 170 patients with chronic migraine were prescribed erenumab in the 3 headache centers. At 3 months, 100/170 (58.8%) had 50% or greater reduction in monthly migraine days. At 6 months, 79/170 (46.5%) had 50% or greater reduction in monthly migraine days. At 6 months, there was a mean reduction in monthly headache days of 9.2 days, a mean reduction in monthly migraine days of 10.2 days. There were few adverse events reported. Conclusion: This is the first report from 3 Australian headache centers about erenumab in the real world. Our analysis has supported erenumab as an effective and well‐tolerated migraine preventative therapy for patients with chronic migraine who have failed many preventative therapies. [ABSTRACT FROM AUTHOR]

Polydopamine (PD) and melanin species are chemically complex systems, the formation and properties of which are incompletely understood. Inspired by the role of functional amyloids in melanin biosynthesis, this paper examines the influences of the supramolecular structure of amyloids on oxidative polymerization of dopamine. Kinetic analyses on the formation of PD species in the presence of hen egg white lysozyme (HEWL) fibers or soluble HEWL revealed that both forms gave rise to the total quantity of PD species, but the rate of their formation could be accelerated only by the amyloid form. PD species formed with HEWL fibers showed a morphology of bundled fibers, whereas those with soluble HEWL had a mesh‐like structure. Amyloid fibers of recombinant Pmel17 had properties similar to those of HEWL fibers in modulating PD formation. The results presented here suggest how nature designs functionality with an amyloid structure and can help understand and engineer chemistries of other functional amyloids. [ABSTRACT FROM AUTHOR]

Peptides stimulating synthesis of extracellular matrix are now commonly used in the production of anti‐ageing cosmetics. However, much uncertainty still exists about the methodology of their clinical assessment. The aim of the study was to review the literature for clinical study designs assessing the efficacy of these peptides. The authors searched systematically publications indexed in PubMed, Scope and Web of Science, according to the PRISMA protocol. Altogether 12 scientific papers, reporting results of 15 independent studies were identified. Out of these 15 studies, only six used a placebo control. Double‐blinding was applied in five out of 15 studies. Nine studies were based on female‐only populations. For the product performance evaluation, most of the studies (10 out of the 15) used image‐based methods. The literature on the topic is sparse. The studies carried out so far have many methodological limitations. Most of the clinical experiments hitherto conducted were non‐double‐blind and used no placebo control. There is a need for better planned and controlled clinical trials in this area. [ABSTRACT FROM AUTHOR]

A histidine‐containing bola‐amphiphilic molecule (NDIP) containing a peptide‐appended naphthalenediimide (NDI) forms fluorescent hydrogels in phosphate buffer and organogels with benzenoid solvents. These gels were characterized by several spectroscopic and microscopic techniques including FT‐IR, HR‐TEM, powder X‐ray diffraction and small‐angle X‐ray scattering, UV‐Vis and fluorescence studies. The gelator molecule exhibits no significant fluorescence in the xerogel state, while it shows a significant fluorescence (bright cyan) in the presence of volatile organic/inorganic acid vapors; this cyan color vanishes in presence of base (ammonia vapors). A reusable paper‐strip‐based method based on this self‐assembled fluorescent material can be used to easily detect hazardous volatile acid and base vapors with the naked eye. [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]

The new GnRH‐Ιanalogue developed in this paper was based on the D‐Trp6‐GnRH‐Ι‐scaffold, and its potency was increased by the replacement Gly‐NH2 by NH‐NH2 binding to the Gly at position 10. Triptorelin‐Hydrazide analogue was synthesized using solid phase. For 111In labeling, synthesized peptide was followed by conjugation with DOTA using pSCN‐Bn‐DOTA. The conjugated Triptorelin‐Hydrazide was labeled with 500‐550 MBq of 111In‐chloride (in 0.2 M HCl). At optimized conditions after labeling, radio‐chromatography showed radiochemical purity of approximately equal to 98% (RTLC) and greater than 95% (HPLC). The serum stability of the tracer was determined up to 24 hr. Binding affinities of Triptorelin‐Hydrazide analogue were determined in a binding assay for both human and rat GnRH receptors. For in vivo studies, 111In‐peptide was injected intravenously via the tail vein into rats and significant ovaries uptake consist with reported GnRH receptor mappings. In vitro radioligand binding assays performed with GnRHR‐expressing human cell lines using 125I‐Triptorelin as the standard radioligand. The quantities of internalization efficiency and receptor affinity of the new radioligand were IC50 = 0.20 ± 0.04 nM vs 0.13 ± 0.08 nM for Triptorelin and internalization: 3.5 ± 0.9% at 1 hr and 12.8 ± 1.8% at 4 hr of the internal reference. The new GnRH‐I analogue was based on the D‐Trp6‐GnRH‐I‐scaffold, and its potency was increased by the replacement Gly‐NH2 by NH‐NH2 binding to the Gly at position 10. For 111In labeling, synthesized peptide was conjugated with pSCN‐Bn‐DOTA. Radio‐chromatography showed radiochemical purity of ≈98% (RTLC) and >95% (HPLC). In vivo studies, 111In‐peptide was shown significant ovaries uptake consist with reported GnRH receptor mappings. In vitro radioligand binding assays performed with GnRHR‐expressing human cell lines using 125I‐Triptorelin as the standard radioligand. [ABSTRACT FROM AUTHOR]

Heterogeneous 1:1 [α/α‐Nα‐Bn‐hydrazino] pseudopeptides are able to self‐organize in CDCl3 solution by an alternation of the γ‐turn and hydrazinoturn conformations. Amidation of the C terminus allowed us to calculate the difference in the chemical shift (Δδ) of the 1H NMR signals of the geminal amidic protons and to associate a Δδ value from 2.58 to 2.75 ppm with the presence of a hydrazinoturn at the C terminus. In this paper we wish to demonstrate that the measurement of a Δδ value close to 0.9 ppm can be correlated with the presence of a γ‐turn structuration. This result will complete this valuable toolbox of Δδ values for a rapid access to the self‐organization of pseudopeptides involving hydrazinoturns and/or γ‐turns based on simple and accessible 1H NMR experiments, and should also provide an opportunity to extend the scope of heterogeneous backbone foldamer design. [ABSTRACT FROM AUTHOR]

Abstract: The reaction mechanism in an active site is of the utmost importance when trying to understand the role that an enzyme plays in biological processes. In a recently published paper [Theor. Chem. Acc. 2017, 136, 86], we formalised the Relative Energy Gradient (REG) method for automating an Interacting Quantum Atoms (IQA) analysis. Here, the REG method is utilised to determine the mechanism of peptide hydrolysis in the aspartic active site of the enzyme HIV‐1 Protease. Using the REG method along with the IQA approach we determine the mechanism of peptide hydrolysis without employing any arbitrary parameters and with remarkable ease (albeit at large computational cost: the system contains 133 atoms, which means that there are 17 689 individual IQA terms to be calculated). When REG and IQA work together it is possible to determine a reaction mechanism at atomistic resolution from data directly derived from quantum calculations, without arbitrary parameters. Moreover, the mechanism determined by this novel method gives concrete insight into how the active site residues catalyse peptide hydrolysis. [ABSTRACT FROM AUTHOR]

Rationale: Protein citrullination (deimination) is a post-translational modification of proteins converting arginine(s) into citrulline(s). "Overcitrullination" could be associated with severe pathological conditions. Mass spectrometric analysis of modified proteins is hindered by several problems. A comprehensive study of the fragmentation of deiminated peptides is not yet available. In this paper we have made an attempt to describe the characteristics of these processes, based on the studies of epitope model oligopeptides derived from clinically relevant proteins. Methods: Solutions of purified model peptides containing either one or two citrulline residues as well as their native variants were injected directly into the electrospray source of a high accuracy and resolution quadrupole-time-of-flight instrument and were analysed by tandem mass spectrometry using low-energy collision-induced dissociation. Results: Loss of isocyanic acid from citrulline residues is a preferred fragmentation route for deiminated peptides, which yields ornithine residues in the sequence. However, simultaneous detection of both the isocyanic acid loss and sequence fragments is often compromised. A preferential cleavage site was observed between citrulline and any other following amino acids yielding intensive complementary b- and y-type ions. Also, citrulline positioned at the C-termini displays a preferential cleavage N-terminal to this residue yielding characteristic y1 ions. These phenomena are described here for the first time and are referred to as the "citrulline effect". Conclusions: We found that the citrulline effect is very pronounced and could be used as a complementary tool for the confirmation of modification sites in addition to losses of isocyanic acids from the protonated molecules or from fragment ions. Low collision energy applied to peptide ions having partially mobile protons reveals the site of modification by generating specific and intensive fragments of the sequence. On the other hand, fragmenting precursor ions with mobile protons usually allows full sequence coverage, although citrulline-specific fragments may exhibit lower intensities compared to other fragments. [ABSTRACT FROM AUTHOR]

Abstract: The peptide segment of prostatic acid phosphatase (PAP248–286) aggregates to form SEVI (semen‐derived enhancer of virus infection) amyloid fibrils. These are characteristic seminal amyloids that have the ability to promote the effect of HIV infection. In this paper, we explore the binding of sulfonated compounds with PAP248–286 through an in silico study. Three derivatives of suramin, NF110, NF279, and NF340, are selected. All of these sulfonated molecules bind to PAP248–286 and alter the conformation of the peptide, even though they have various structures, sizes, and configurations. The compounds bind with PAP248–286 through multiple interactions, such as hydrogen‐bonding interactions, hydrophobic interactions, π–π stacking interactions, and electrostatic interactions. However, NF110, which has an X‐shaped configuration, has the highest binding affinity of the three derivatives investigated. We also perform surface plasmon resonance and a Congo red assay to validate the results. The interactions between PAP248–286 and the sulfonated compounds are proposed to depend on the orientations of the sulfonate groups and the specific configurations of the compounds instead of the number of sulfonate groups. NF110 molecules occupy the exposed binding sites of PAP248–286, blocking interactions between the peptides. Therefore, these compounds are important in inhibiting the aggregation of PAP248–286. Herein, we provide useful information to develop new efficient microbicides to antagonize seminal amyloid fibrils and to block HIV transmission. [ABSTRACT FROM AUTHOR]

A genetic basis for autism spectrum disorder (ASD) is now well established, and with the availability of high-throughput microarray and sequencing platforms, major advances have been made in our understanding of genetic risk factors. Rare, often de novo, copy number and single nucleotide variants are both implicated, with many ASD-implicated genes showing pleiotropy and variable penetrance. Additionally, common variants are also known to play a role in ASD's genetic etiology. These new insights into the architecture of ASD's genetic etiology offer opportunities for the identification of molecular targets for novel interventions, and provide new insight for families seeking genetic counselling.What the Paper Adds: A number of rare genetic variants are implicated in autism spectrum disorder (ASD), with some showing recurrence. Common genetic variants are also important and a number of loci are now being uncovered. Genetic testing for individuals with ASD offers the opportunity to identify relevant genetic etiology. [ABSTRACT FROM AUTHOR]

Proton conduction is an essential process that regulates an integral part of several enzymatic catalyses and bioenergetics. Proton flows in biological entities are sensitively controlled by several mechanisms. To understand and manipulate proton conduction in biosystems, several studies have investigated bulk proton conduction in biomaterials such as polyaspartic acid, collagen, reflectin, serum albumin mats, and eumelanin. However, little is known about the bulk proton conductivity of short peptides and their sequence-dependent behavior. Here, this paper focuses on a short tyrosine-rich peptide that has redox-active and cross-linkable phenol groups. The spin-coated peptide nanofilm is immersed in potassium permanganate solution to induce cross-linking and oxidation, simultaneously leading to hybridization with manganese oxide (MnO x). The peptide/MnO x hybrid nanofilm can efficiently transport protons, and its proton conductivity is ≈18.6 mS cm−1 at room temperature. This value is much higher than that of biomaterials and comparable to those of other synthetic proton-conducting materials. These results suggest that peptide-based hybrid materials can be a promising new class of proton conductor. [ABSTRACT FROM AUTHOR]