Search Results (3,134)

The rapid expansion of peptide libraries and the increasing functional diversity of peptides have highlighted the significance of predicting the multifunctional properties of peptides in bioinformatics research. Although supervised learning methods have made advancements, they typically necessitate substantial amounts of labeled data for yielding accurate prediction. This study presents MvAl-MFP, a multi-label active learning approach that incorporates multiple feature views of peptides. This method takes advantage of the natural properties of multi-view representation for amino acid sequences, meets the requirement of the query-by-committee (QBC) active learning paradigm, and further significantly diminishes the requirement for labeled samples while training high-performing models. First, MvAl-MFP generates nine distinct feature views for a few labeled peptide amino acid sequences by considering various peptide characteristics, including amino acid composition, physicochemical properties, evolutionary information, etc. Then, on each independent view, a multi-label classifier is trained based on the labeled samples. Next, a QBC strategy based on the average entropy of predictions across all trained classifiers is adopted to select a specific number of most valuable unlabeled samples to submit them to human experts for labeling by wet-lab experiments. Finally, the aforementioned procedure is iteratively conducted with a constantly expanding labeled set and updating classifiers until it meets the default stopping criterion. The experiments are conducted on a dataset of multifunctional therapeutic peptides annotated with eight functional labels, including anti-bacterial properties, anti-inflammatory properties, anti-cancer properties, etc. The results clearly demonstrate the superiority of the proposed MvAl-MFP method, as it can rapidly improve prediction performance while only labeling a small number of samples. It provides an effective tool for more precise multifunctional peptide prediction while lowering the cost of wet-lab experiments. Full article

Background/Objectives: Antimicrobial resistance (AMR) contributes to millions of deaths globally each year, creating an urgent need for new therapeutic agents. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their potential to combat AMR pathogens. This study aimed to evaluate the antimicrobial activity of an AMP from a soil-derived bacterial isolate against Gram-negative bacteria. Method: Soil bacteria were isolated and screened for antimicrobial activity. The bioactive peptide was purified and determined its structure and antimicrobial efficacy. Genomic analysis was conducted to predict the biosynthetic gene clusters (BGCs) responsible for AMP production. Results: Genomic analysis identified the isolate as Paenibacillus sp. Na14, which exhibited low genomic similarity (61.0%) to other known Paenibacillus species, suggesting it may represent a novel species. The AMP from the Na14 strain exhibited heat stability up to 90 °C for 3 h and retained its activity across a broad pH range from 3 to 11. Structural analysis revealed that the Na14 peptide consisted of 14 amino acid residues, adopting an α-helical structure. This peptide exhibited bactericidal activity at concentrations of 2–4 µg/mL within 6–12 h, and its killing rate was concentration-dependent. The peptide was found to disrupt the bacterial membranes. The Na14 peptide shared 64.29% sequence similarity with brevibacillin 2V, an AMP from Brevibacillus sp., which also belongs to the Paenibacillaceae family. Genomic annotation identified BGCs associated with secondary metabolism, with a particular focus on non-ribosomal peptide synthetase (NRPS) gene clusters. Structural modeling of the predicted NRPS enzymes showed high similarity to known NRPS modules in Brevibacillus species. These genomic findings provide evidence supporting the similarity between the Na14 peptide and brevibacillin 2V. Conclusions: This study highlights the discovery of a novel AMP with potent activity against Gram-negative pathogens and provides new insight into conserved AMP biosynthetic enzymes within the Paenibacillaceae family. Full article

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Bamboo shoot boiled liquid (BSBL), a processing byproduct containing soluble proteins, peptides, amino acids, carbohydrates, and phenolics, is typically discarded, causing resource waste and environmental issues. This study analyzed metabolic changes in BSBL during Pediococcus pentosaceus B49 fermentation. The result of partial least squares discriminant analysis (PLS-DA) revealed significant metabolite profile differences across fermentation times (0 h, 24 h, 48 h, 72 h, 96 h). The most substantial alterations occurred within the first 24 h, followed by stabilization. Compared to unfermented BSBL, fermented samples exhibited significantly elevated signal intensities for 5,7-dimethoxyflavone, cinnamic acid, 3,4-dihydro-2H-1-benzopyran-2-one, 6,8-dimethyl-4-hydroxycoumarin, and 2-hydroxycinnamic acid (p < 0.05), showing upward trends over time. Conversely, (+)-gallocatechin intensity decreased gradually. Bitter peptides, such as alanylisoleucine, isoleucylisoleucine, leucylvaline, and phenylalanylisoleucine, in BSBL exhibited a significant reduction following fermentation with P. pentosaceus B49 (p < 0.05). KEGG enrichment indicated tyrosine metabolism (ko00350) and arginine/proline metabolism (ko00330) as the most impacted pathways. These findings elucidate metabolic regulation in BSBL fermentation, supporting development of functional fermented bamboo products. Full article

TasA gene, encoding a functional amyloid protein critical for biofilm formation and antimicrobial activity, was cloned from the endophytic strain Bacillus amyloliquefaciens BS-3, isolated from rubber tree roots. This study identified the shortest functional TasA variant (483 bp, 160 aa) reported to date, featuring unique amino acid substitutions in conserved domains. Bioinformatics analysis predicted a signal peptide (1–27 aa) and transmembrane domain (7–29 aa), which were truncated to optimize heterologous expression. Two prokaryotic vectors (pET28a and pCZN1) were constructed, with pCZN1-TasA expressed solubly in Escherichia coli Arctic Express at 15 °C, while pET28a-TasA formed inclusion bodies at 37 °C. Purified recombinant TasA exhibited potent antifungal activity, achieving 98.6% ± 1.09 inhibition against Colletotrichum acutatum, 64.77% ± 1.34 against Alternaria heveae. Notably, TasA completely suppressed spore germination in C. acutatum and Oidium heveae Steinmannat 60 μg/mL. Structural analysis via AlphaFold3 revealed that truncation enhanced protein stability. These findings highlight BS-3-derived TasA as a promising biocontrol agent, providing molecular insights for developing protein-based biopesticides against rubber tree pathogens. Full article

Carboxypeptidase A4 (CPA4) is an exopeptidase that cleaves peptide bonds at the C-terminal domain within peptides and proteins. It preferentially cleaves peptides with terminal aromatic or branched chain amino acid residues such as phenylalanine, tryptophan, or leucine. CPA4 was first discovered in prostate cancer cells, but it is now known to be expressed in various tissues throughout the body. Its physiologic expression is governed by latexin, a noncompetitive endogenous inhibitor of CPA4. Nevertheless, the overexpression of CPA4 has been associated with the progression and aggressiveness of many malignancies, including prostate, pancreatic, breast and lung cancer, to name a few. CPA4’s role in cancer has been attributed to its disruption of many cellular signaling pathways, e.g., PI3K-AKT-mTOR, STAT3-ERK, AKT-cMyc, GPCR, and estrogen signaling. The dysregulation of these pathways by CPA4 could be responsible for inducing epithelial--mesenchymal transition (EMT), tumor invasion and drug resistance. Although CPA4 has been found to regulate cancer aggressiveness and poor prognosis, no comprehensive review summarizing the role of CPA4 in cancer is available so far. In this review, we provide a brief description of peptidases, their classification, history of CPA4, mechanism of action of CPA4 as a peptidase, its expression in various tissues, including cancers, its role in various tumor types, the associated molecular pathways and cellular processes. We further discuss the limitations of current literature linking CPA4 to cancers and challenges that prevent using CPA4 as a biomarker for cancer aggressiveness and predicting drug response and highlight a number of future strategies that can help to overcome the limitations. Full article

Recent advancements have been made in the precise prediction of protein structures within the Protein Folding Problem (PFP), particularly in relation to minimizing the energy function to achieve stable and biologically relevant protein structures. This problem is classified as NP-hard within computational theory, necessitating the development of various techniques and algorithms. Bio-inspired algorithms have proven effective in addressing NP-hard challenges in practical applications. This study introduces a novel hybrid algorithm, termed GRSABio, which integrates the strategies of Jumping Spider Algorithm (JSOA) with the Golden Ratio Simulated Annealing (GRSA) for peptide prediction. Furthermore, the GRSABio algorithm incorporates a Convolutional Neural Network for fragment prediction (FCNN), forms an enhanced methodology called GRSABio-FCNN. This integrated framework achieves improved structure refinement based on energy for protein prediction. The proposed enhanced GRSABio-FCNN approach was applied to a dataset of 60 peptides. The Wilcoxon and Friedman statistics test were employed to compare the GRSABio-FCNN results against recent state-of-the-art-approaches. The results of these tests indicate that the GRSABio-FCNN approach is competitive with state-of-the-art methods for peptides up to 50 amino acids in length and surpasses leading PFP algorithms for peptides with up to 30 amino acids. Full article

Background/Objectives: The clinical potential of antimicrobial peptides (AMPs) against dual threats like antimicrobial resistance (AMR) and cancer is often limited by their high host cell toxicity. Here, we focused on brevinin-2OS (B2OS), a novel peptide from the skin of Odorrana schmackeri with potent haemolytic activity. The objective was to study the structure–activity relationship and optimise the safety via targeted modifications. Methods: A dual-modification strategy involving C-terminal truncation and subsequent N-terminal D-amino acid substitution was employed. The bioactivities and safety profiles of the resulting analogues were evaluated using antimicrobial, haemolysis, and cytotoxicity assays. Result: Removal of the rana box in B2OS(1-22)-NH₂ substantially reduced haemolysis while maintaining bioactivities. Remarkably, the D-leucine substitution in [D-Leu²]B2OS(1-22)-NH₂ displayed a superior HC₅₀ value of 118.1 µM, representing a more than ten-fold improvement compared to its parent peptide (HC₅₀ of 10.44 µM). This optimised analogue also demonstrated faster bactericidal kinetics and enhanced membrane permeabilisation, leading to a greater than 22-fold improvement in its therapeutic index against Gram-positive bacteria. Conclusions: The C-terminal rana box is a primary determinant of toxicity rather than a requirement for activity in the B2OS scaffold. The engineered peptide [D-Leu²]B2OS(1-22)-NH₂ emerges as a promising lead compound, and this dual-modification strategy provides a powerful design principle for developing safer, more effective peptide-based therapeutics. Full article

Hypertension is a major pathogenic contributor to cardiovascular diseases, primarily mediated through activation of the angiotensin-converting enzyme (ACE) system. Food-derived ACE-inhibitory peptides represent a promising alternative to synthetic drugs due to their favorable safety profile and minimal side effects. ACE-inhibitory peptides have been extensively identified from various foods, with their antihypertensive activity and molecular mechanisms comprehensively characterized through in vitro and in vivo studies. ACE-inhibitory peptides can be prepared by methods such as natural extraction, enzymatic hydrolysis, and fermentation. The production process significantly modulates structural characteristics of the polypeptides including peptide chain length, amino acid composition, and sequence, consequently determining their functional activity. To comprehensively elucidate the gastrointestinal stability and mechanisms action of ACE-inhibitory peptides, integrated experimental approaches combining both in vitro and in vivo methodologies are essential. This review systematically examines current advances in food-derived ACE-inhibitory peptides in terms of sources, production, structure, in vivo and in vitro activities, and bioavailability. Full article

Background: Bovine babesiosis, caused by the tick-borne apicomplexan parasite Babesia spp., is an economically significant disease that threatens the cattle industry worldwide. Babesia bovis is the most pathogenic species, leading to high morbidity and mortality in infected animals. One promising approach to vaccination against bovine babesiosis involves the use of multiple protective antigens, offering advantages over traditional live-attenuated vaccines. Tools such as immunobioinformatics and reverse vaccinology have facilitated the identification of novel antigens. Enolase, a “moonlighting” enzyme of the glycolytic pathway with demonstrated vaccine potential in other pathogens, has not yet been studied in B. bovis. Methods: In this study, the enolase gene from two B. bovis isolates was successfully identified and sequenced. The gene, consisting of 1366 base pairs, encodes a predicted protein of 438 amino acids. Its expression in intraerythrocytic parasites was confirmed by RT-PCR. Two peptides containing predicted B-cell epitopes were synthesized and used to immunize rabbits. Hyperimmune sera were then analyzed by ELISA, confocal microscopy, Western blot, and an in vitro neutralization assay. Results: The hyperimmune sera showed high antibody titers, reaching up to 1:256,000. Specific antibodies recognized intraerythrocytic merozoites by confocal microscopy and bound to a ~47 kDa protein in erythrocytic cultures of B. bovis as detected by Western blot. In the neutralization assay, antibodies raised against peptide 1 had no observable effect, whereas those targeting peptide 2 significantly reduced parasitemia by 71.99%. Conclusions: These results suggest that B. bovis enolase contains B-cell epitopes capable of inducing neutralizing antibodies and may play a role in parasite–host interactions. Enolase is therefore a promising candidate for further exploration as a vaccine antigen. Nonetheless, additional experimental studies are needed to fully elucidate its biological function and validate its vaccine potential. Full article

Background: Peptides are a class of molecules that can be presented as good antimicrobials and with mechanisms that avoid resistance, and the design of peptides with good activity can be complex and laborious. The study of their quantitative structure–activity relationships through machine learning algorithms can shed light on a rational and effective design. Methods: Information on the antimicrobial activity of peptides was collected, and their structures were characterized by molecular descriptors generation to design regression and classification models based on machine learning algorithms. The contribution of each descriptor in the generated models was evaluated by determining its relative importance and, finally, the antimicrobial activity of new peptides was estimated. Results: A structured database of antimicrobial peptides and their descriptors was obtained, with which 56 machine learning models were generated. Random Forest-based models showed better performance, and of these, regression models showed variable performance (R² = 0.339–0.574), while classification models showed good performance (MCC = 0.662–0.755 and ACC = 0.831–0.877). Those models based on bacterial groups showed better performance than those based on the entire dataset. The properties of the new peptides generated are related to important descriptors that encode physicochemical properties such as lower molecular weight, higher charge, propensity to form alpha-helical structures, lower hydrophobicity, and higher frequency of amino acids such as lysine and serine. Conclusions: Machine learning models allowed to establish the structure–activity relationships of antimicrobial peptides. Classification models performed better than regression models. These models allowed us to make predictions and new peptides with high antimicrobial potential were proposed. Full article

Antimicrobial peptides (AMPs) provide a robust alternative to conventional antibiotics, combating escalating microbial resistance through their diverse functions and broad pathogen-targeting abilities. While current deep learning technologies enhance AMP generation, they face challenges in developing multifunctional AMPs due to intricate amino acid interdependencies and limited consideration of diverse functional activities. To overcome this challenge, we introduce a novel de novo multifunctional AMP design framework that enhances a Feedback Generative Adversarial Network (FBGAN) by integrating a global quantitative AMP activity regression module and a multifunctional-attribute integrated prediction module. This integrated approach not only facilitates the automated generation of potential AMP candidates, but also optimizes the network’s ability to assess their multifunctionality. Initially, by integrating an effective pre-trained regression and classification model with feedback-loop mechanisms, our model can not only identify potential valid AMP candidates, but also optimizes computational predictions of Minimum Inhibitory Concentration (MIC) values. Subsequently, we employ a combinatorial predictor to simultaneously identify and predict five multifunctional AMP bioactivities, enabling the generation of multifunctional AMPs. The experimental results demonstrate the efficiency of generating AMPs with multiple enhanced antimicrobial properties, indicating that our work can provide a valuable reference for combating multi-drug-resistant infections. Full article

MOTS-c is a mitochondrial peptide that plays a crucial role in regulating energy metabolism, gene expression, and immune processes. However, current research primarily focuses on mammals like humans and mice, with no reports on avian MOTS-c. This study aimed to identify and characterize MOTS-c coding sequences across major poultry species through bioinformatics analysis and experimental validation. The alignment results showed high sequence similarity in the MOTS-c coding regions between avian and mammalian species. However, a single nucleotide deletion was identified in avian sequences at the position corresponding to the fourth amino acid residue of mammalian homologs, resulting in divergent downstream amino acid sequences. Despite this deletion, several residues were conserved across species. Phylogenetic analysis of mRNA sequences grouped pigeons with mammals, while protein sequence analysis revealed that poultry and mammals form separate branches, highlighting the divergence between avian and mammalian MOTS-c sequences. Tissue expression profiling demonstrated widespread distribution of chicken MOTS-c across multiple tissues, with the highest expression levels in the heart. Fasting significantly reduced heart MOTS-c expression, suggesting potential metabolic regulatory functions. Functional analysis of MOTS-c in primary hepatocytes revealed significant enrichment of the ribosome, oxidative phosphorylation, and key signaling pathways (PI3K-AKT and JAK-STAT) following 24 hours of treatment. Western blot validation confirmed MOTS-c-mediated activation of the AKT signaling pathway. This study represents the first comprehensive characterization of avian MOTS-c, providing critical insights into its evolutionary conservation and its potential functional roles in gene expression and cellular metabolism. Our findings establish a foundation for further investigation into the functions of mitochondrial-encoded peptides in avian species. Full article

Cell proliferation plays a pivotal role in multiple physiological processes, including osteoporosis alleviation, wound healing, and immune enhancement. Numerous novel peptides with cell proliferation-promoting activity have been identified. These peptides exert their functions by modulating key cellular signaling pathways, thereby regulating diverse biological processes related to cell proliferation. This work summarizes peptides derived from animals and plants that stimulate cell proliferation, focusing on their amino acid composition, physicochemical properties, and preparation techniques. Furthermore, we highlight the major signaling pathways—such as the PI3K/Akt, MAPK/ERK, and Wnt/β-catenin pathways—that have been implicated in the mechanistic studies of food-derived peptides. Through the analysis and summary of previous studies, we observe a notable lack of in vivo animal models and clinical trials, indicating that these may represent promising directions for future research on food-derived bioactive peptides. Meanwhile, the potential safety concerns of proliferation-enhancing peptides—such as immunogenicity, appropriate dosage, and gastrointestinal stability—warrant greater attention. In summary, this review provides a comprehensive overview of the sources and mechanisms of cell proliferation-promoting peptides and addresses the challenges in industrializing bioactive peptide-based functional foods; therefore, further research in this area is encouraged. Full article

Phospholipase A1 (Ves a 1), a major toxin from Vespa affinis venom, poses significant risks to allergic individuals. Nevertheless, the epitope determinants of Ves a 1 have not been characterized. Thus, identifying its linear B-cell epitopes is crucial for understanding envenomation mechanisms. In this study, we predicted and identified B-cell epitopes EP5 and EP6 as potential candidates. EP5 formed an α-helix at the active site of Ves a 1, whereas EP6 adopted an extended loop conformation. Both synthetic peptides were synthesized and evaluated for their inhibitory effects using immune-inhibitory assays with polyclonal antibodies (pAbs) targeting both native (nVes a 1) and recombinant (rVes a 1) forms. The Ves a 1 polyclonal antibodies (pAb-nVes a 1 and pAb-Ves a 1) were produced, and their specificity binding to Ves a 1 was confirmed by Western blot. Next, ELISA inhibition assays showed that EP5 and EP6 significantly blocked pAb binding to both nVes a 1 and rVes a 1. Dot blot and Western blot assays supported these findings, particularly with stronger inhibition toward rVes a 1. Furthermore, enzymatic assays indicated that nVes a 1 and rVes a 1 retained phospholipase activity. Immunoinformatics docking showed that EP5 and EP6 specifically bind to a single-chain variable fragment antibody (scFv) targeting Naja naja PLA2. Molecular analysis revealed similar amino acid interactions to the template, suggesting effective paratope–epitope binding. These results support the potential of EP5 and EP6 for future diagnosis and therapy of V. affinis venom allergy. Full article