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

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

Cancer is the second leading cause of death globally, but conventional anticancer drugs have side effects, mainly due to their non-specific distribution in the body in both cancerous and healthy cells. To address this relevant issue and improve the efficiency of anticancer drugs, increasing attention is being devoted to hydrogel drug-delivery systems for different kinds of cancer treatment due to their high biocompatibility and stability, low side effects, and ease of modifications. To improve the therapeutic efficiency and provide multi-functionality, different types of nanoparticles (NPs) can be incorporated within the hydrogels to form smart hydrogel nanocomposites, benefiting the advantages of both counterparts and suitable for advanced anticancer applications. Despite many papers on non-peptide hydrogel nanocomposites, there is limited knowledge about peptide-based nanocomposites, specifically in anti-cancer drug delivery. The aim of this short but comprehensive review is, therefore, to focus attention on the synergies resulting from the combination of NPs with peptide-based hydrogels. This review, which includes a survey of recent advances in this kind of material, does not aim to be an exhaustive review of hydrogel technology, but it instead highlights recent noteworthy publications and discusses novel perspectives to provide valuable insights into the promising synergic combination of peptide hydrogels and NPs for the design of novel anticancer drug delivery systems. [ABSTRACT FROM AUTHOR]

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

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

This paper presents an investigation of liposome deformation and shape distortion using four membrane-binding peptides: TAT and C105Y as cell-penetrating peptides (CPPs), and melittin and ovispirin as antimicrobial peptides (AMPs). Liposome deformation was monitored utilizing fluorescent microscopy, while the binding of peptides to the DOPC membrane was estimated through capacitance measurements. The degree of liposome deformation and shape distortion was found to be higher for the CPPs compared to the AMPs. Additionally, it was observed that C105Y did not induce liposome rupture, unlike the other three peptides. We propose that these variations in liposome distortion may be attributed to differences in secondary structure, specifically the presence of an α-helix or random coil. Our studies offer insight into the use of peptides to elicit control of liposome architecture and may offer a promising approach for regulating the bodies of liposomal molecular robots. [ABSTRACT FROM AUTHOR]

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

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

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

Utilization of beneficial components from food industry waste is a very promising endeavor, which is in line with the circular economy and sustainable development. Brewer's spent yeast, as one of the major brewing by-products, has a wealth of high-value materials such as β-glucans and peptides. β-glucans are derived from the cell wall and possess immunomodulatory and prebiotic properties, which are considered healthy for consumption due to their yeast-derived nature. Some studies have shown that yeast peptides have bioactivities such as hypotensive and antioxidant activities and have been utilized in large quantities in the food industry as flavor substances. This paper reviews recent research on the extraction methods, bioactivities, and applications in food of brewer's spent yeast β-glucans and peptides. The article also summarizes the challenges of utilizing the high-value components of BSY and offers an outlook for future work. Overall, this paper provides a basis for the future comprehensive utilization of brewer's spent yeast. [ABSTRACT FROM AUTHOR]

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

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

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

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]

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

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

Ovarian adenocarcinoma is the gynecological malignancy with the worst prognosis and the highest mortality rate. In the first stages of treatment, chemotherapy results effective, but its prolonged use and high doses lead to the appearance of resistance to treatments and relapse in most patients, representing a major challenge for clinicians. We developed PEP-010, a cell penetrating proapoptotic peptide disrupting the protein-protein interaction between caspase-9 and protein phosphatase 2A, thereby leading to the recovery of their activity in the apoptotic pathway. MTT assay or Annexin-V/Propidium Iodide staining and flow cytometry analysis were used to assess sensitivity to chemotherapies and apoptosis after treatment with PEP-010 in monotherapy or in combination with paclitaxel in ovarian carcinoma cell lines. DNA damage was assessed by immunofluorescence using γH2AX marker. We show here that PEP-010 effectively induces cell death in monotherapy on in up to 55% of cells from ovarian adenocarcinoma cell models resistant to different chemotherapies. Moreover, when used in combination with paclitaxel, one of the therapeutic options for recurrent ovarian carcinoma, PEP-010 showed a beneficial effect leading to the reduction of the IC50 of paclitaxel of 2.2 times and to apoptosis in 87% of cells. The described results suggest the potential therapeutic interest for PEP-010 and lead to the choice of ovarian adenocarcinoma as one of the major indications of the ongoing clinical trial. [ABSTRACT FROM AUTHOR]

Secreted signaling peptides are central regulators of growth, development, and stress responses, but specific steps in the evolution of these peptides and their receptors are not well understood. Also, the molecular mechanisms of peptide-receptor binding are only known for a few examples, primarily owing to the limited availability of protein structural determination capabilities to few laboratories worldwide. Plants have evolved a multitude of secreted signaling peptides and corresponding transmembrane receptors. Stress-responsive SERINE RICH ENDOGENOUS PEPTIDES (SCOOPs) were recently identified. Bioactive SCOOPs are proteolytically processed by subtilases and are perceived by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) in the model plant Arabidopsis thaliana. How SCOOPs and MIK2 have (co)evolved, and how SCOOPs bind to MIK2 are unknown. Using in silico analysis of 350 plant genomes and subsequent functional testing, we revealed the conservation of MIK2 as SCOOP receptor within the plant order Brassicales. We then leveraged AI-based structural modeling and comparative genomics to identify two conserved putative SCOOP-MIK2 binding pockets across Brassicales MIK2 homologues predicted to interact with the "SxS" motif of otherwise sequence-divergent SCOOPs. Mutagenesis of both predicted binding pockets compromised SCOOP binding to MIK2, SCOOP-induced complex formation between MIK2 and its coreceptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1, and SCOOP-induced reactive oxygen species production, thus, confirming our in silico predictions. Collectively, in addition to revealing the elusive SCOOP-MIK2 binding mechanism, our analytic pipeline combining phylogenomics, AI-based structural predictions, and experimental biochemical and physiological validation provides a blueprint for the elucidation of peptide ligand-receptor perception mechanisms. [ABSTRACT FROM AUTHOR]

Dynamic wrinkle reduction continues to challenge aesthetic dermatology, predominantly addressed through Botulinumtoxin (Botox) injections. Despite Botox's robust efficacy with up to an 80% reduction in wrinkle visibility within just one week, its invasive administration and specific mechanism of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex inhibition prompt the exploration of safer, non-invasive alternatives. This review critically assesses recent innovations in non-invasive effects, with a focus on peptides and botanical extracts that exhibit a diverse array of mechanisms including SNARE complex inhibition, modulation of calcium and sodium channels, and interactions with acetylcholine receptors, contributing to their effectiveness in muscle relaxation on dynamic wrinkle approaches. Noteworthy peptides such as Argireline and SYN-Ake replicate the neuromodulatory effects of Botox, achieving up to a 52% reduction in wrinkles within four weeks without injections. Moreover, botanical extracts meet the rising demand for clean beauty solutions by enhancing skin elasticity and health through gentle yet potent mechanisms. However, the main concern with peptides is their low absorption rate, with only six clinical validations regarding Botox-like peptide anti-wrinkle efficacy available. These advancements not only deepen our understanding of cosmetic dermatology but also significantly influence market dynamics and consumer behavior, underscoring their pivotal role in redefining the future landscape of anti-aging effects. [ABSTRACT FROM AUTHOR]

Histones are keys to many epigenetic events and their complexes have therapeutic and diagnostic importance. The determination of the structures of histone complexes is fundamental in the design of new drugs. Computational molecular docking is widely used for the prediction of target–ligand complexes. Large, linear peptides like the tail regions of histones are challenging ligands for docking due to their large conformational flexibility, extensive hydration, and weak interactions with the shallow binding pockets of their reader proteins. Thus, fast docking methods often fail to produce complex structures of such peptide ligands at a level appropriate for drug design. To address this challenge, and improve the structural quality of the docked complexes, post-docking refinement has been applied using various molecular dynamics (MD) approaches. However, a final consensus has not been reached on the desired MD refinement protocol. In this present study, MD refinement strategies were systematically explored on a set of problematic complexes of histone peptide ligands with relatively large errors in their docked geometries. Six protocols were compared that differ in their MD simulation parameters. In all cases, pre-MD hydration of the complex interface regions was applied to avoid the unwanted presence of empty cavities. The best-performing protocol achieved a median of 32% improvement over the docked structures in terms of the change in root mean squared deviations from the experimental references. The influence of structural factors and explicit hydration on the performance of post-docking MD refinements are also discussed to help with their implementation in future methods and applications. [ABSTRACT FROM AUTHOR]

The discovery of new peptides and their derivatives is an outcome of ongoing efforts to identify a peptide with significant biological activity for effective usage as a possible therapeutic agent. Spinorphin peptides have been documented to exhibit numerous applications and features. In this study, biologically active peptide derivatives based on novel peptide analogues of spinorphin conjugated with 5,5′-dimethyl (Dm) and 5,5′-diphenyl (Ph) hydantoin derivatives have been successfully synthesized and characterized. Scanning electron microscopy (SEM) and spectral methods such as UV-Vis, FT-IR (Fourier Transform Infrared Spectroscopy), CD (Circular Dichroism), and fluorimetry were used to characterize the microstructure of the resulting compounds. The results revealed changes in peptide morphology as a result of the restructuring of the aminoacidic sequences and aromatic bonds, which is related to the formation of intermolecular hydrogen bonds between tyrosyl groups and the hydantoin moiety. Electrochemical and fluorescence approaches were used to determine some physicochemical parameters related to the biological behavior of the compounds. The biological properties of the spinorphin derivatives were evaluated in vivo for anticonvulsant activity against the psychomotor seizures at different doses of the studied peptides. Both spinorphin analog peptides with Ph and Dm groups showed activity against all three phases of the seizure in the intravenous Pentylenetetrazole Seizure (ivPTZ) test. This suggests that hydantoin residues do not play a crucial role in the structure of spinorphin compounds and in determining the potency to raise the seizure threshold. On the other hand, analogs with a phenytoin residue are active against the drug-resistant epilepsy test (6-Hz test). In addition, bioactivity analyses revealed that the new peptide analogues have the potential to be used as antimicrobial and antioxidant compounds. These findings suggest promising avenues for further research that may lead to the development of alternative medicines or applications in various fields beyond epilepsy treatment. [ABSTRACT FROM AUTHOR]

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF‐EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment. [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome system is essential to all eukaryotes and has been shown to be critical to parasite survival as well, including Plasmodium falciparum, the causative agent of the deadliest form of malarial disease. Despite the central role of the ubiquitin-proteasome pathway to parasite viability across its entire life-cycle, specific inhibitors targeting the individual enzymes mediating ubiquitin attachment and removal do not currently exist. The ability to disrupt P. falciparum growth at multiple developmental stages is particularly attractive as this could potentially prevent both disease pathology, caused by asexually dividing parasites, as well as transmission which is mediated by sexually differentiated parasites. The deubiquitinating enzyme PfUCHL3 is an essential protein, transcribed across both human and mosquito developmental stages. PfUCHL3 is considered hard to drug by conventional methods given the high level of homology of its active site to human UCHL3 as well as to other UCH domain enzymes. Here, we apply the RaPID mRNA display technology and identify constrained peptides capable of binding to PfUCHL3 with nanomolar affinities. The two lead peptides were found to selectively inhibit the deubiquitinase activity of PfUCHL3 versus HsUCHL3. NMR spectroscopy revealed that the peptides do not act by binding to the active site but instead block binding of the ubiquitin substrate. We demonstrate that this approach can be used to target essential protein-protein interactions within the Plasmodium ubiquitin pathway, enabling the application of chemically constrained peptides as a novel class of antimalarial therapeutics. [ABSTRACT FROM AUTHOR]

(1) Autophagy plays a significant role in development and cell proliferation. This process is mainly accomplished by the LC3 protein, which, after maturation, builds the nascent autophagosomes. The inhibition of LC3 maturation results in the interference of autophagy activation. (2) In this study, starting from the structure of a known LC3B binder (LIR2-RavZ peptide), we identified new LC3B ligands by applying an in silico drug design strategy. The most promising peptides were synthesized, biophysically assayed, and biologically evaluated to ascertain their potential antiproliferative activity on five humans cell lines. (3) A cyclic peptide (named Pep6), endowed with high conformational stability (due to the presence of a disulfide bridge), displayed a Kd value on LC3B in the nanomolar range. Assays accomplished on PC3, MCF-7, and A549 cancer cell lines proved that Pep6 exhibited cytotoxic effects comparable to those of the peptide LIR2-RavZ, a reference LC3B ligand. Furthermore, it was ineffective on both normal prostatic epithelium PNT2 and autophagy-defective prostate cancer DU145 cells. (4) Pep6 can be considered a new autophagy inhibitor that can be employed as a pharmacological tool or even as a template for the rational design of new small molecules endowed with autophagy inhibitory activity. [ABSTRACT FROM AUTHOR]

In situ depot gel is a type of polymeric long-acting injectable (pLAI) drug delivery system; compared to microsphere technology, its preparation process is simpler and more conducive to industrialization. To ensure the chemical stability of peptide ACTY116, we avoided the use of harsh conditions such as high temperatures, high shear mixing, or homogenization; maintaining a water-free and oxygen-free environment was also critical to prevent hydrolysis and oxidation. Molecular dynamics (MDs) simulations were employed to assess the stability mechanism between ACTY116 and the pLAI system. The initial structure of ACTY116 with an alpha helix conformation was constructed using SYBYL-X, and the copolymer PLGA was generated by AMBER 16; results showed that PLGA-based in situ depot gel improved conformational stability of ACTY116 through hydrogen bonds formed between peptide ACTY116 and the components of the pLAI formulation, while PLGA (Poly(DL-lactide-co-glycolide)) also created steric hindrance and shielding effects to prevent conformational changes. As a result, the chemical and conformational stability and in vivo long-acting characteristics of ACTY116 ensure its enhanced efficacy. In summary, we successfully achieved our objective of developing a highly stable peptide-loaded long-acting injectable (LAI) in situ depot gel formulation that is stable for at least 3 months under harsh conditions (40 °C, above body temperature), elucidating the underlying stabilisation mechanism, and the high stability of the ACTY116 pLAI formulation creates favourable conditions for its in vivo pharmacological activity lasting for weeks or even months. [ABSTRACT FROM AUTHOR]

Wound healing is a complicated and multistage biological process for the repair of damaged/injured tissues, which requires intelligent designs to provide comprehensive and convenient treatment. Peptide‐based wound dressings have received extensive attention for further development and application due to their excellent biocompatibility and multifunctionality. However, the current lack of intuitive analysis of the development trend and research hotspots of peptides applied in wound healing, as well as detailed elaboration of possible research hotspots, restricted obtaining a comprehensive understanding and development in this field. The present study analysed publications from the Web of Science (WOS) Core Collection database and visualized the hotspots and current trends of peptide research in wound healing. Data between January 1st, 2003, and December 31st, 2022, were collected and subjected to a bibliometric analysis. The countries, institutions, co‐authorship, co‐citation reference, and co‐occurrence of keywords in this subject were examined using VOSviewer and CiteSpace. We provided an intuitive, timely, and logical overview of the development prospects and challenges of peptide application in wound healing and some solutions to the major obstacles, which will help researchers gain insights into the investigation of this promising field. [ABSTRACT FROM AUTHOR]

The potential of bisphenol A (BPA)-binding peptides fused to magnetic beads is demonstrated as novel adsorbents that are reusable and highly selective for BPA removal from aqueous environments, in which various interfering substances coexist. Magnetic beads harboring peptides (peptide beads) showed a higher BPA removal capacity (8.6 mg/g) than that of bare beads without peptides (2.0 mg/g). The BPA adsorption capacity of peptide beads increased with the number of peptides fused onto the beads, where monomeric, dimeric, or trimeric repeats of a BPA-binding peptide were fused to magnetic beads. The BPA-adsorbing beads were regenerated using a methanol–acetic acid mixture, and after six regeneration cycles, the adsorption capacity remained above 87% of its initial capacity. The selective removal of BPA was confirmed in the presence of BPA analogs with high structural similarity (bisphenol F and bisphenol S) or in synthetic wastewater. The present work is a pioneering study that investigates the selective affinity of peptides to remove specific organics with high selectivity from complex environmental matrices. [ABSTRACT FROM AUTHOR]

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

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

Background: Several methods were introduced for enamel biomimetic remineralization that utilize a biomimetic analogue to interact and absorb bioavailable calcium and phosphate ions and induce crystal nucleation on demineralized enamel. Amelogenin is the most predominant enamel matrix protein that is involved in enamel biomineralization. It plays a major role in developing the enamel's hierarchical microstructure. Therefore, this study was conducted to evaluate the ability of an amelogenin-inspired peptide to promote the remineralization potential of fluoride and a supersaturated calcium phosphate solution in treating artificially induced enamel carious lesions under pH-cycling regimen. Methods: Fifty enamel slices were prepared with a window (4*4 mm2) on the surface. Five samples were set as control healthy enamel and 45 samples were subjected to demineralization for 3 days. Another 5 samples were set as control demineralized enamel and 40 enamel samples were assigned into 8 experimental groups (n=5) (P/I, P/II, P/III, P/AS, NP/I, NP/II, NP/III and NP/AS) according to peptide treatment (peptide P or non-peptide NP) and remineralizing solution used (I; calcium phosphate solution, II; calcium phosphate fluoride solution, III; fluoride solution and AS; artificial saliva). Samples were then subjected to demineralization/remineralization cycles for 9 days. Samples in all experimental groups were evaluated using Raman spectroscopy for mineral content recovery percentage, microhardness and nanoindentation as healthy, demineralized enamel and after pH-cycling. Data were statistically analysed using two-way repeated measures Anova followed by Bonferroni-corrected post hoc test for pairwise multiple comparisons between groups. Statistical significance was set at p= 0.05. Additionally, XRD, FESEM and EDXS were used for crystal orientation, surface morphology and elemental analysis after pH-cycling. Results: Nanocrystals clumped in a directional manner were detected in peptide-treated groups. P/II showed the highest significant mean values in mineral content recovery (63.31%), microhardness (268.81±6.52 VHN), elastic modulus (88.74±2.71 GPa), nanohardness (3.08±0.59 GPa) and the best crystal orientation with I002/I300 (1.87±0.08). Conclusion: Despite pH changes, the tested peptide was capable of remineralizing enamel with ordered crystals. Moreover, the supplementary use of calcium phosphate fluoride solution with peptide granted an enhancement in enamel mechanical properties after remineralization. [ABSTRACT FROM AUTHOR]

Background: Fatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (18F) for positron emission tomography (PET) applications, and evaluate the binding of the radiolabeled ACooP in human tumor tissue sections with high FABP3 expression. Results: The prosthetic compound 6-[18F]fluoronicotinic acid 4-nitrophenyl ester was conveniently prepared with an on-resin 18F-fluorination in 29.9% radiochemical yield and 96.6% radiochemical purity. Interestingly, 6-[18F]fluoronicotinic acid 4-nitrophenyl ester conjugated to ACooP exclusively by S-acylation instead of the expected N-acylation, and the chemical identity of the product [18F]FNA-S-ACooP was confirmed. In the in vitro binding experiments, [18F]FNA-S-ACooP exhibited heterogeneous and high focal binding in malignant tissue sections, where we also observed abundant FABP3 positivity by immunofluorescence staining. Blocking study further confirmed the [18F]FNA-S-ACooP binding specificity. Conclusions: FABP3 targeted ACooP peptide was successfully radiolabeled by S-acylation using 6-[18F]fluoronicotinic acid 4-nitrophenyl ester as the prosthetic compound. The tissue binding and blocking studies together with anti-FABP3 immunostaining confirmed [18F]FNA-S-ACooP binding specificity. Further preclinical studies of [18F]FNA-S-ACooP are warranted. [ABSTRACT FROM AUTHOR]

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino-acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1–4 h resulted in 1.9- to 2.4-fold increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx) but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, which paves the way for research on the biological roles of hemocyte peptides in chordates. [ABSTRACT FROM AUTHOR]

In mineral processing, arsenic-bearing minerals are particularly difficult to separate from their non-arsenic counterparts because they possess similar surface properties. Peptides are well known for their target specificity and can offer a 'green' alternative to traditional flotation reagents. However, the use of peptide technologies in mineral processing for developing novel flotation reagents has not been explored. Hence, this work aims to develop a screening method to identify mineral-binding peptides as potential reagent candidates. It is hypothesised that peptides can selectively adsorb onto mineral surfaces, and this method can efficiently identify mineral-binding peptides with high specificity toward the target minerals. The methodology presented involves a selection of peptide candidates from existing literature that show affinity toward arsenic species. These peptides were tested for their adsorption performance onto selected mineral surfaces to evaluate their mineral selectivity under flotation conditions. The study demonstrates that the screening method developed is effective in identifying peptides that have an affinity for target minerals, in this case, arsenic minerals. The screening method can be applied to other minerals, thus, unlocking the potential for developing new reagent chemistries for use in mineral processing. [ABSTRACT FROM AUTHOR]

Peptide-functionalized nanomedicine, which addresses the challenges of specificity and efficacy in drug delivery, is emerging as a pivotal approach for cancer therapy. Globally, cancer remains a leading cause of mortality, and conventional treatments, such as chemotherapy, often lack precision and cause adverse effects. The integration of peptides into nanomedicine offers a promising solution for enhancing the targeting and delivery of therapeutic agents. This review focuses on the three primary applications of peptides: cancer cell-targeting ligands, building blocks for self-assembling nanostructures, and elements of stimuli-responsive systems. Nanoparticles modified with peptides improved targeting of cancer cells, minimized damage to healthy tissues, and optimized drug delivery. The versatility of self-assembled peptide structures makes them an innovative vehicle for drug delivery by leveraging their biocompatibility and diverse nanoarchitectures. In particular, the mechanism of cell death induced by self-assembled structures offers a novel approach to cancer therapy. In addition, peptides in stimuli-responsive systems enable precise drug release in response to specific conditions in the tumor microenvironment. The use of peptides in nanomedicine not only augments the efficacy and safety of cancer treatments but also suggests new research directions. In this review, we introduce systems and functionalization methods using peptides or peptide-modified nanoparticles to overcome challenges in the treatment of specific cancers, including breast cancer, lung cancer, colon cancer, prostate cancer, pancreatic cancer, liver cancer, skin cancer, glioma, osteosarcoma, and cervical cancer. [ABSTRACT FROM AUTHOR]

When the skin is damaged, accelerating the repair of skin trauma and promoting the recovery of tissue function are crucial considerations in clinical treatment. Previously, we isolated and identified an active peptide (livisin) from the skin secretion of the frog Odorrana livida. Livisin exhibited strong protease inhibitory activity, water solubility, and stability, yet its wound-healing properties have not yet been studied. In this study, we assessed the impact of livisin on wound healing and investigated the underlying mechanism contributing to its effect. Our findings revealed livisin effectively stimulated the migration of keratinocytes, with the underlying mechanisms involved the activation of CaSR as a peptide calcium mimetic. This activation resulted in the stimulation of the CaSR/E-cadherin/EGFR/ERK signaling pathways. Moreover, the therapeutic effects of livisin were partially reduced by blocking the CaSR/E-cadherin/EGFR/ERK signaling pathway. The interaction between livisin and CaSR was further investigated by molecular docking. Additionally, studies using a mouse full-thickness wound model demonstrated livisin could accelerate skin wound healing by promoting re-epithelialization and collagen deposition. In conclusion, our study provides experimental evidence supporting the use of livisin in skin wound healing, highlighting its potential as an effective therapeutic option. [ABSTRACT FROM AUTHOR]

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

Understanding how to formulate peptides into metered dose inhalers (MDIs) is a bottleneck issue hampering the clinical translation of relevant products. In our previous studies, a bottom–up method to prepare peptide-containing particles for MDIs was reported. Nevertheless, the formation mechanism of the particles remains unclear. In this work, considering the production workflow, a confinement–segregation theory was put forward as a hypothesis to explain the formation mechanism. Confinement and segregation were two major processes during formation, and their definitions are provided in detail. Based on the theory, some factors influencing particle formation were also discussed, which promoted future formulation design. It is believed that the proposed theory will provide new insights into the study of peptide-containing MDIs and boost their clinical translation. [ABSTRACT FROM AUTHOR]

In this work, we developed two new polyfunctional hybrid systems in which the presence of Fc redox "antennas" on peptide scaffolds allows for a modulation of their electronic properties. Specifically, we synthesized two helical hexapeptides containing four Aib (α-amionoisobutyric acid) and two L-Dap (2,3-diamino propionic acid) residues. L-Dap side chains were then functionalized with Fc moieties. The structures of the two 310 helical peptides, namely Z-Aib-L-Dap(Fc)-Aib-Aib-L-Dap(Fc)-Aib-NH-iPr and Z-Aib-L-Dap(Fc)-Aib-L-Dap(Fc)-Aib-Aib-NH-iPr, were investigated by X-ray diffraction, 2D-NMR, CD and IR spectroscopies. Due to the helical conformation, in Z-Aib-L-Dap(Fc)-Aib-Aib-L-Dap(Fc)-Aib-NH-iPr, the Fc groups are located on the same face of the helix, but in Z-Aib-L-Dap(Fc)-Aib-L-Dap(Fc)-Aib-Aib-NH-iPr, they are located on opposite faces. Surprisingly, two bands were found through DPV for Z-Aib-L-Dap(Fc)-Aib-L-Dap(Fc)-Aib-Aib-NH-iPr, indicating an electrostatic interaction between the Fc groups despite their longer reciprocal distance with respect to that in Z-Aib-L-Dap(Fc)-Aib-Aib-L-Dap(Fc)-Aib-NH-iPr. CD experiments at different concentrations evidenced aggregation for Z-Aib-L-Dap(Fc)-Aib-L-Dap(Fc)-Aib-Aib-NH-iPr, even at high dilutions, thus suggesting that the Fc-Fc electrostatic interaction could be of an intermolecular nature. [ABSTRACT FROM AUTHOR]

Antiangiogenic therapy with sorafenib (SF) alone is ineffective in eradicating tumors, and its long-term application can exacerbate tumor hypoxia, which in turn restricts SF's therapeutic efficacy. Here, a redox-responsive fluorinated peptide (DEN-TAT-PFC) consisting of dendritic poly-lysine, cell-penetrating peptide TAT, and perfluorocarbon was designed and synthesized to co-load siRNA-targeting hypoxia-inducible factors (siHIF-1α) and SF. The unique architecture of the peptide and fluorinated modifications enhanced the siRNA delivery efficiency, including increased siRNA binding, GSH-responsive release, cellular uptake, endosomal escape, and serum resistance. Simultaneously, the DEN-TAT-PFC/SF/siHIF-1α co-delivery system achieved efficient knockdown of HIF-1α at mRNA and protein levels, thus alleviating hypoxia and further substantially reducing VEGF expression. Additionally, the excellent oxygen-carrying ability of DEN-TAT-PFC may facilitate relief of the hypoxic microenvironment. As a result of these synergistic effects, DEN-TAT-PFC/SF/siHIF-1α exhibited considerable anti-tumor cell proliferation and anti-angiogenesis effects. Therefore, DEN-TAT-PFC can be a versatile platform for fabricating fluorine-containing drugs/siRNA complex nano-systems. [ABSTRACT FROM AUTHOR]

Background: Cancer, being a complex disease, presents a major challenge for the scientific and medical communities. Peptide therapeutics have played a significant role in different medical practices, including cancer treatment. Method: This review provides an overview of the current situation and potential development prospects of anticancer peptides (ACPs), with a particular focus on peptide vaccines and peptide-drug conjugates for cancer treatment. Results: ACPs can be used directly as cytotoxic agents (molecularly targeted peptides) or can act as carriers (guiding missile) of chemotherapeutic agents and radionuclides by specifically targeting cancer cells. More than 60 natural and synthetic cationic peptides are approved in the USA and other major markets for the treatment of cancer and other diseases. Compared to traditional cancer treatments, peptides exhibit anticancer activity with high specificity and the ability to rapidly kill target cancer cells. ACP's target and kill cancer cells via different mechanisms, including membrane disruption, pore formation, induction of apoptosis, necrosis, autophagy, and regulation of the immune system. Modified peptides have been developed as carriers for drugs, vaccines, and peptide–drug conjugates, which have been evaluated in various phases of clinical trials for the treatment of different types of solid and leukemia cancer. Conclusions: This review highlights the potential of ACPs as a promising therapeutic option for cancer treatment, particularly through the use of peptide vaccines and peptide–drug conjugates. Despite the limitations of peptides, such as poor metabolic stability and low bioavailability, modified peptides show promise in addressing these challenges. Various mechanism of action of anticancer peptides. Modes of action against cancer cells including: inducing apoptosis by cytochrome c release, direct cell membrane lysis (necrosis), inhibiting angiogenesis, inducing autophagy-mediated cell death and immune cell regulation. [ABSTRACT FROM AUTHOR]

Enzymes of the radical S-adenosyl-l-methionine (radical SAM, RS) superfamily, the largest in nature, catalyze remarkably diverse reactions initiated by H-atom abstraction. Glycyl radical enzyme activating enzymes (GRE-AEs) are a growing class of RS enzymes that generate the catalytically essential glycyl radical of GREs, which in turn catalyze essential reactions in anaerobic metabolism. Here, we probe the reaction of the GRE-AE pyruvate formate-lyase activating enzyme (PFL-AE) with the peptide substrate RVSG734YAV, which mimics the site of glycyl radical formation on the native substrate, pyruvate formate-lyase. Time-resolved freeze-quench electron paramagnetic resonance spectroscopy shows that at short mixing times reduced PFL-AE + SAM reacts with RVSG734YAV to form the central organometallic intermediate, O, in which the adenosyl 5'C is covalently bound to the unique iron of the [4Fe-4S] cluster. Freeze-trapping the reaction at longer times reveals the formation of the peptide G734• glycyl radical product. Of central importance, freeze-quenching at intermediate times reveals that the conversion of O to peptide glycyl radical is not concerted. Instead, homolysis of the O Fe-C5' bond generates the nominally "free" 5'-dAdo• radical, which is captured here by freeze-trapping. During cryoannealing at 77 K, the 5'-dAdo• directly abstracts an H-atom from the peptide to generate the G734• peptide radical trapped in the PFL-AE active site. These observations reveal the 5'-dAdo• radical to be a well-defined intermediate, caught in the act of substrate H-atom abstraction, providing new insights into the mechanistic steps of radical initiation by RS enzymes. [ABSTRACT FROM AUTHOR]

Most biocatalytic processes in eukaryotic cells are regulated by subcellular microenvironments such as membrane-bound or membraneless organelles. These natural compartmentalization systems have inspired the design of synthetic compartments composed of a variety of building blocks. Recently, the emerging field of liquid-liquid phase separation has facilitated the design of biomolecular condensates composed of proteins and nucleic acids, with controllable properties including polarity, diffusivity, surface tension, and encapsulation efficiency. However, utilizing phase-separated condensates as optical sensors has not yet been attempted. Here, we were inspired by the biosynthesis of melanin pigments, a key biocatalytic process that is regulated by compartmentalization in organelles, to design minimalistic biomolecular condensates with emergent optical properties. Melanins are ubiquitous pigment materials with a range of functionalities including photoprotection, coloration, and free radical scavenging activity. Their biosynthesis in the confined melanosomes involves oxidation-polymerization of tyrosine (Tyr), catalyzed by the enzyme tyrosinase. We have now developed condensates that are formed by an interaction between a Tyr-containing peptide and RNA and can serve as both microreactors and substrates for tyrosinase. Importantly, partitioning of Tyr into the condensates and subsequent oxidation-polymerization gives rise to unique optical properties including far-red fluorescence. We now demonstrate that individual condensates can serve as sensors to detect tyrosinase activity, with a limit of detection similar to that of synthetic fluorescent probes. This approach opens opportunities to utilize designer biomolecular condensates as diagnostic tools for various disorders involving abnormal enzymatic activity. [ABSTRACT FROM AUTHOR]

Peptides are short linear molecules consisting of amino acids that play an essential role in most biological processes. They can treat diseases by working as a vaccine or antimicrobial agent and serves as a cancer molecule to deliver the drug to the target site for the treatment of cancer. They have the potential to solve the drawbacks of current medications and can be industrially produced in large quantities at low cost. However, poor chemical and physical stability, short circulating plasma half-life, and solubility are some issues that need solutions before they can be used as therapeutics. PepAnalyzer tool is a user-friendly tool that predicts 15 different properties such as binding potential, half-life, transmembrane patterns, test tube stability, charge, isoelectric point, molecular weights, and molar extinction coefficients only using the sequence. The tool is designed using BioPython utility and has even results with standard tools, such as Expasy, EBI, Genecorner, and Geneinfinity. The tool assists students, researchers, and the pharmaceutical sector. The PepAnalyzer tool's online platform is accessible at the link: http://www.iksmbrlabdu.in/peptool. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress-induced retinal degeneration is among the main contributing factors of serious ocular pathologies that can lead to irreversible blindness. αB-crystallin (cry) is an abundant component of the visual pathway in the vitreous humor, which modulates protein and cellular homeostasis. Within this protein exists a 20 amino acid fragment (mini-cry) with both chaperone and antiapoptotic activity. This study fuses this mini-cry peptide to two temperature-sensitive elastin-like polypeptides (ELP) with the goal of prolonging its activity in the retina. Methods: The biophysical properties and chaperone activity of cry-ELPs were confirmed by mass spectrometry, cloud-point determination, and dynamic light scattering 'DLS'. For the first time, this work compares a simpler ELP architecture, cry-V96, with a previously reported ELP diblock copolymer, cry-SI. Their relative mechanisms of cellular uptake and antiapoptotic potential were tested using retinal pigment epithelial cells (ARPE-19). Oxidative stress was induced with H2O2 and comparative internalization of both cry-ELPs was made using 2D and 3D culture models. We also explored the role of lysosomal membrane permeabilization by confocal microscopy. Results: The results indicated successful ELP fusion, cellular association with both 2D and 3D cultures, which were enhanced by oxidative stress. Both constructs suppressed apoptotic signaling (cleaved caspase-3); however, cry-V96 exhibited greater lysosomal escape. Conclusions: ELP architecture is a critical factor to optimize delivery of therapeutic peptides, such as the anti-apoptotic mini-cry peptide; furthermore, the protection of mini-cry via ELPs is enhanced by lysosomal membrane permeabilization. [ABSTRACT FROM AUTHOR]

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

Osteoarthritis (OA) is the most common joint disorder, with a social and financial burden that is expected to increase in the coming years. Currently, there are no effective medications to treat it. Due to limited treatment options, patients often resort to supplements, such as collagen hydrolysates (CHs). CHs are products with low molecular weight (MW) peptides, often between 3 and 6 kDa, and are a result of industrialized processed collagen. Collagen extraction is often a by-product of the meat industry, with the main source for collagen-based products being bovine, although it can also be obtained from porcine and piscine sources. CHs have demonstrated positive results in clinical trials related to joint health, such as decreased joint pain, increased mobility, and structural joint improvements. The bioactivity of CHs is primarily attributed to their bioactive peptide (BAP) content. However, there are significant knowledge gaps regarding the digestion, bioavailability, and bioactivity of CH-derived BAPs, and how different CH products compare in that regard. The present review discusses CHs and their BAP content as potential treatments for OA. [ABSTRACT FROM AUTHOR]

It is critical to find an alternative therapeutic approach to combat Pseudomonas aeruginosa (P. aeruginosa) that can simultaneously reduce the occurrence of bacterial resistance. The tetraspanin CD9, a highly expressed membrane protein in melanocytes was chosen for this study because it is highly expressed in keratinocytes and has been implicated in the pathogenesis of bacterial infections in a previous study. The antimicrobial activity of CD9 peptides against the standard strain P. aeruginosa (ATCC 27853) and a clinical multidrug-resistant P. aeruginosa (MDR- P. aeruginosa) was studied using the disc diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CD9 peptides were determined by broth microdilution assays with concentrations ranging from 1 mg/mL to 4.88x10-4 mg/mL. The antibiofilm activity of the CD9 peptides was also determined. CD9 peptides showed an 11.75 ± 2.36 mm inhibition zone against the standard P. aeruginosa strain but none against the MDR- P. aeruginosa. Both isolates had the same MIC value, 0.25 mg/mL. The MBC for the standard strain P. aeruginosa was 0.5 mg/mL, while for the MDR- P. aeruginosa strain, it was 1 mg/mL. CD9 peptides significantly inhibited up to 70% biofilm against both P. aeruginosa isolates. CD9 peptides showed a modest inhibitory effect against the standard strain P. aeruginosa but not against MDR- P. aeruginosa. Interestingly, CD9 peptides were found to be a good anti-biofilm treatment against both P. aeruginosa isolates. This study demonstrated that CD9 peptides have the potential to be an alternative antimicrobial treatment against P. aeruginosa. [ABSTRACT FROM AUTHOR]

Bacterial infections seriously threaten human safety. Therefore, it is very important to develop a method for bacterial detection and treatment with rapid response, high sensitivity, and simple operation. A peptide CF4KYP (C, cysteine; F4, phenylalanine tetrapeptide; K, lysine; YP, phosphorylated tyrosine) functionalized gold nanoparticle (AuNPs-CF4KYP) was synthesized for simultaneous detection and treatment of bacteria based on bacterial alkaline phosphatase (ALP). In solution, ALP can induce AuNPs-CF4KYP aggregation and produce significant color changes. After encountering bacteria, monodisperse AuNPs-CF4KYP can aggregate/assemble in situ on the surface of the bacterial membrane, change the color of the solution from wine red to grey, destroy the bacterial membrane structure, and induce the production of a large number of reactive oxygen species within the bacteria. The absorption change of AuNPs-CF4KYP solution has a good linear relationship with the number of bacteria. Furthermore, the aggregation of AuNPs-CF4KYP kills approximately 80% of Salmonella typhimurium. By combining enzyme-instructed peptide self-assembly technology and colorimetric analysis technology, we achieve rapid and sensitive colorimetric detection and killing of bacteria. [ABSTRACT FROM AUTHOR]

We report the discovery of a straightforward protocol to convert phenols into the corresponding aryl triflates using 1‐methyl‐3‐((trifluoromethyl)sulfonyl)‐1,3‐dihydro‐2H‐benzo[d]imidazol‐2‐one in the presence of a fluoride source. This novel reagent can be handled without any precautions to exclude air or moisture making this method highly convenient. The reactions generally show very clean conversions within only a few minutes at room temperature. The mild conditions allow the so far unprecedented O‐triflation of tyrosine in peptides bearing challenging side chains present for example in arginine and histidine including the late‐stage triflation of complex bioactive peptides. We show how aryl triflates – an interesting but so far underutilized group – can be used to optimize physicochemical and in vitro properties of compound series in medicinal chemistry. We believe that this method is highly attractive for applications in peptide functionalization as well as automated and medicinal chemistry. [ABSTRACT FROM AUTHOR]

Background and Purpose: Repeated amino acid sequences in proteins are widely found, and the glycine–serine–alanine repeat is an element with a general propensity to form β‐sheet aggregates as found in key pathological factors, in several neurodegenerative diseases. Such properties of this repeat may guide development of disease‐modifying therapies for neurodegenerative disease. However, details of its role and underlying mechanism(s) remain largely unknown. Experimental Approach: Actions of specific glycine–serine–alanine repeat peptides (SNPs), especially SNP‐9, on Alzheimer's disease (AD)‐like abnormalities were evaluated in transgenic mice and Caenorhabditis elegans, and in rat and cell models. Entry of SNPs into the brain, SNP activity in neuronal cells and peptide entry into cells were analysed in vivo and in vitro. Cell‐free systems and the yeast two‐hybrid system were also used to explore possible targets of SNP‐9, and interactions of potential targets with SNP‐9 were confirmed in cell‐based systems. Key Results: We first identified SNP‐9 as a potent neuroprotective peptide with the activity to decrease oligomeric amyloid β (Aβ) via co‐assembling with the toxic Aβ oligomer to form hetero‐oligomers. Also, calcyclin‐binding protein was found to act as a SNP‐9‐binding protein, by screening of a human brain cDNA library. Such binding showed that SNP‐9 could regulate the abnormal hyperphosphorylation of tau via calcyclin‐binding protein. Conclusion and Implications: Our study provides a foundation for development of SNPs, especially SNP‐9, as potential therapeutic interventions for AD. We propose SNP‐9 as a potential therapeutic agent for the treatment of AD. [ABSTRACT FROM AUTHOR]