{"title":"Plant-derived Cyclotides in Immunomodulation and their Therapeutic Potential.","authors":"Reema Mishra, Preeti Agarwal, Anshita Sharma, Meenal Mittal, Pooja Gulati, Aparajita Mohanty","doi":"10.2174/0109298665364479250214101422","DOIUrl":"10.2174/0109298665364479250214101422","url":null,"abstract":"<p><p>The incidences of immune-related disorders have drastically increased in recent years across the world population. Treatment and management of these diseases, especially autoimmune disorders, are complex and challenging. Available synthetic drugs are not completely effective and also pose serious side effects for the patients. Cyclotides are a class of plant-derived cyclic peptides (28-37 amino acids) with three conserved disulfide linkages establishing a cyclic cystine knot (CCK) motif that makes them very stable biomolecules. Their inherent stability, bioavailability and membrane-penetrating capabilities render them attractive potential pharmacological agents. Studies have demonstrated that cyclotides can either enhance or suppress immune responses, making them versatile candidates for treating various immune-related disorders. Of more than 1000 cyclotides discovered to date, only up to 15 native cyclotides (e.g. kalata B1, pase and caripe cyclotides) have been screened to demonstrate their immunomodulatory activity. Of special significance is the chemically synthesised lysine mutant of kalata B1 viz. [T20K], where preclinical studies have shown promise in the treatment of the autoimmune disorder, multiple sclerosis. In vivo studies in mice models have demonstrated that daily administration of 1mg/day of [T20K] led to a significant decrease in the level of cytokine secretion, lesser demyelination (<1%) and very low inflammatory index (<0.5), in the immunized mice. Moreover, when compared with other immunosuppressive drugs (azathioprine, prednisolone, and cyclosporine A) there was a notable drop in mortality and morbidity in mice administered with [T20K]. The cyclotides, kalata B1 and MCoTI-I have also been used as scaffolds to graft bioactive peptides with immunomodulatory activity. Subsequent in vitro and in vivo studies of these grafted cyclotides have demonstrated their therapeutic ability. Keeping in view the therapeutic potential of cyclotides as immunomodulatory peptides, the present review discusses its current research scenario and implications for the future in tackling immune-related disorders.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"3-15"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cleverson Diniz Teixeira de Freitas, Jefferson Soares de Oliveira
{"title":"Use of Plant Peptidases for the Production of Therapeutic Peptides.","authors":"Cleverson Diniz Teixeira de Freitas, Jefferson Soares de Oliveira","doi":"10.2174/0109298665373399250319082357","DOIUrl":"10.2174/0109298665373399250319082357","url":null,"abstract":"<p><p>Peptidases play crucial roles in numerous physiological processes within living organisms. Therefore, they have been employed in various pharmaceutical applications. Plant peptidases have attracted considerable attention in various areas due to their specificity, stability across a diverse range of pH and temperatures, and safety profile. Here, we have focused on the use of plant peptidases, mostly papain and bromelain, to produce biologically active peptides, which confer various health advantages, including antioxidant, antimicrobial, antihypertensive, analgesic, antidiabetic, and anti-inflammatory effects. We have also discussed the importance of the action mechanism of peptidases for generating bioactive peptides with specific sequences and functions, the ecological and sustainability benefits of plant-derived peptidases compared to animal alternatives, digestive stability and bioavailability of peptides, as well as some obstacles to the commercialization of bioactive peptides and key challenges in peptidase-based industrial applications. Finally, we have examined enzyme immobilization as a viable method to enhance the production of bioactive peptides, offering numerous advantages in both research and industry contexts.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"16-31"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Developments, Challenges in Bitter Gourd Protein and Peptide Extraction Strategies, Techno-Functional Properties, Bioaccessibility, and Commercial Applications.","authors":"Tawseefa Jan, Rajvinder Kour, Seerat Sharma, Imran Sheikh, Ajar Nath Yadav, Naseer Ahmed","doi":"10.2174/0109298665403605260209062701","DOIUrl":"10.2174/0109298665403605260209062701","url":null,"abstract":"<p><p>Bitter gourd (Momordica charantia L.) has turned out to be a significant source of proteins and bioactive peptides, which have prospects of finding application in functional foods and nutraceuticals. It contains a high level of proteins and phytochemicals, which offer significant health benefits. Leaves, seeds, and stems are also high sources of antioxidants and are good stores of important nutrients. It can help prevent and treat a number of lifestyle-related diseases such as diabetes mellitus, cancer, nephrolithiasis, scabies, abdominal pain, and fever. This review critically evaluates the latest developments in methods of extraction of proteins and peptides from bitter gourd and emphasizes innovative methods. Such methods have enhanced extraction efficiency and protein yield, and improved functional properties. However, there are still issues in optimizing these processes to make them bioavailable and provide stable products. Furthermore, the commercial feasibility of bitter gourd proteins is limited by cost, flexibility, and marketability. This review highlights the need for research to improve extraction methods, explore new uses, and overcome trade barriers.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"226-243"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unravelling Proteomic Pathways: Mechanistic Insights into Schiff Base-Mediated Disruption of Microbial Protein Integrity and Antimicrobial Potential.","authors":"Jatin Kishore Sharma, Sushil Kumar","doi":"10.2174/0109298665415763251208083026","DOIUrl":"10.2174/0109298665415763251208083026","url":null,"abstract":"<p><p>Proteins are essential to the survival and pathogenicity of microorganisms, serving as structural components, enzymes, and regulatory elements. Schiff bases, organic compounds formed by the condensation of primary amines with carbonyl compounds, have emerged as promising antimicrobial agents due to their ability to disrupt microbial protein integrity. This study investigates the multifaceted interactions between Schiff bases and microbial proteins, revealing key mechanistic insights such as membrane disruption, enzyme inhibition, metal chelation, and Reactive Oxygen Species (ROS) generation. Notably, Schiff bases demonstrate potent activity against multidrug-resistant strains, including Staphylococcus aureus, Escherichia coli, and Candida albicans, and exhibit synergistic effects when combined with conventional antibiotics. Proteomic analysis highlights their impact on survival-associated and pathogenicity-related proteins, including chaperones, efflux pumps, and virulence factors. These findings underscore the novelty of targeting microbial proteomes and stress-response pathways, positioning Schiff bases as versatile candidates for next-generation antimicrobial therapies.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 1","pages":"63-78"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stress Management and Therapeutic Prospects of Glutathione Reductase as a Shared Antioxidant in Plants and Animals.","authors":"Rashmi Pratap Singh, Nandini Sarkar","doi":"10.2174/0109298665439617260330100906","DOIUrl":"10.2174/0109298665439617260330100906","url":null,"abstract":"<p><p>In both plants and animals, Glutathione Reductase (GR) is recognized as a key antioxidant enzyme. Owing to its diverse roles in stress response and therapeutic applications, this enzyme has recently drawn significant research interest. GR plays a vital role in maintaining cellular redox homeostasis and protecting cells from oxidative damage, thereby contributing to overall human health. It facilitates the conversion of oxidized Glutathione (GSSG) into its reduced form (GSH), a critical antioxidant molecule essential for numerous cellular processes. Beyond its core biochemical function, GR serves as an important model system for investigating redox regulation and flavoprotein catalysis. Clinically, the enzyme is associated with various pathological conditions, including oxidative stress-related disorders, diabetes mellitus, cardiovascular diseases, and neurodegenerative disorders. The enzyme's multifaceted functionality has broad implications in biomedical research, clinical therapeutics, and the development of novel treatment strategies. In plants, GR plays a pivotal role in responses to environmental stresses such as drought, salinity, heavy metal toxicity, and pathogen attack. Its activity contributes to the advancement of crop improvement strategies and enhances our understanding of cellular defence mechanisms under stress conditions. It also serves as an important biomarker for stress in plants. The level of GR expression or enzymatic activity is often used as an indicator of the plant's oxidative stress status and its capacity to tolerate adverse conditions. Monitoring GR provides vital data on plant health. This paper provides a detailed analysis of glutathione reductase's biochemical principles, physiological roles in plant and animal systems, significance in stress reduction, and prospective therapeutic applications.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 2","pages":"397-408"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design and TAG-Assisted Synthesis of the C-Terminal Amidated Antimicrobial Peptide NCBP-1 Derived from a Plant-Derived Noncanonical NCBP and Its Biological Activity.","authors":"Ziying Geng, Linyan Zhang, Haidi Li, Taigang Liang","doi":"10.2174/0109298665465381260330113137","DOIUrl":"10.2174/0109298665465381260330113137","url":null,"abstract":"<p><strong>Introduction: </strong>The rise in global bacterial resistance necessitates the discovery of novel antibiotics. Plant-derived Antimicrobial Peptides (AMPs) offer structural diversity and biocompatibility. This study aims to investigate the green synthesis and biological activities of derivatives of NCBP, a linear non-classical AMP identified from plants.</p><p><strong>Methods: </strong>Five NCBP derivatives (NCBP-1 to NCBP-5) were generated using a green tag-assisted peptide synthesis (TAPS) strategy, combined with site-directed mutagenesis and terminal modification. The peptides were characterized by MS and HPLC and subsequently evaluated for antibacterial activity against ten bacterial strains, salt tolerance, and cytotoxicity in RAW 264.7 murine macrophages. Molecular docking was performed to assess binding interactions.</p><p><strong>Results: </strong>NCBP-1 was identified as the lead derivative, demonstrating potent antibacterial activity (MIC 8 μg·mL-¹) and low cytotoxicity. It also exhibited moderate anti-inflammatory activity in LPSstimulated RAW 264.7 macrophages. Its antibacterial mechanism was further supported by favorable molecular docking interactions with E. coli outer membrane LPS (PDB ID: 4RHB).</p><p><strong>Discussion: </strong>The combined approach successfully identified NCBP-1 as a potent antibacterial candidate. Its activity against Gram-negative bacteria is likely related to LPS binding, as suggested by the docking results. Further studies would be needed to fully elucidate its mechanism of action.</p><p><strong>Conclusion: </strong>NCBP-1 represents a promising lead for the development of novel antibacterial agents, particularly for treating Gram-negative bacterial infections.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 2","pages":"465-479"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to: Reviewing the Context of Molecular Modeling to Enhance the Application of Machine Learning Technologies for Safer Bioinformatics.","authors":"Márcio V Ramos","doi":"10.2174/0929866533999260326091022","DOIUrl":"10.2174/0929866533999260326091022","url":null,"abstract":"<p><p>After publication of this article [1], minor production error is identified, an incorrect link was displayed under Heading 4. This error has now been corrected. The original article can be found online at: https://www.benthamscience.com/article/152908 Details of the errors and the corrections are provided here. Original: When calculating properties related to this function, such as the interaction energy between ligand and receptor in docking, instead of using the entire Cartesian space, the computational effort is substantially reduced since only the grid points are used for these calculations [14]. (https://doi.org/10.1002/jcc.21256). Corrected: When calculating properties related to this function, such as the interaction energy between ligand and receptor in docking, instead of using the entire Cartesian space, the computational effort is substantially reduced since only the grid points are used for these calculations [14].</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 1","pages":"395"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Creativity, Sustainability, and Education Driving the Future of Protein and Peptide Research.","authors":"Anna Maria Papini","doi":"10.2174/0109298665465880251128114438","DOIUrl":"https://doi.org/10.2174/0109298665465880251128114438","url":null,"abstract":"","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 1","pages":"xiii"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minghui Tian, Yemeng Zhang, Xiaolei Liu, Xiaoyu Liu, Wei Li
{"title":"Peptide Extract from Apricot Kernels Mitigates Damage in Human Aortic Endothelial Cells Induced by Polystyrene Microplastics through the Inhibition of the NLRP3 Signaling Pathway.","authors":"Minghui Tian, Yemeng Zhang, Xiaolei Liu, Xiaoyu Liu, Wei Li","doi":"10.2174/0109298665410365251118113915","DOIUrl":"10.2174/0109298665410365251118113915","url":null,"abstract":"<p><strong>Introduction: </strong>Polystyrene microplastics (PS-MPs) contribute to cardiovascular pathologies by inducing vascular endothelial injury through oxidative stress and inflammation. This study aimed to investigate the protective role of apricot kernel peptide extract (AKPE) against PS-MPs- induced damage in human aortic endothelial cells (HAECs) and to elucidate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>AKPE was isolated from apricot kernels using an activity-guided fractionation approach based on its protective efficacy in HAECs exposed to PS-MPs. Cytotoxicity and dose-response experiments established an optimal concentration of 20 μM. Subsequent analyses included cell viability (CCK-8 assay), intracellular reactive oxygen species (ROS) and superoxide dismutase (SOD) activity, inflammatory cytokine levels (α, IL-1β, IL-18) via ELISA, apoptosis assessment by flow cytometry, and evaluation of mitochondrial function. Bioactive oligopeptides within AKPE were identified by mass spectrometry. The involvement of the NLRP3 inflammasome and Wnt/β-catenin signaling pathways was examined using Western blotting and quantitative PCR.</p><p><strong>Results: </strong>AKPE significantly counteracted the PS-MPs-induced reduction in HAEC viability, increasing it by 16.2% (p < 0.01). It also reduced intracellular ROS levels by 35.1% (p < 0.01) while preserving SOD activity. Furthermore, AKPE suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-18) by 17-38% (p < 0.01). PS-MPs-induced mitochondrial dysfunction and apoptosis were markedly attenuated, with a 39.1% decrease in apoptotic cells (p < 0.01). Mass spectrometry identified eight key oligopeptides as the primary bioactive constituents of AKPE. Mechanistically, these components acted synergistically to inhibit NLRP3 inflammasome activation and to modulate the dysregulated Wnt/β-catenin pathway.</p><p><strong>Discussion: </strong>AKPE protects HAECs from PS-MPs-induced damage through dual mechanisms: (1) suppressing NLRP3 inflammasome-driven inflammation and (2) mitigating oxidative stress via Wnt/β-catenin pathway inhibition. The synergy among AKPE peptides enhances resilience against PS-MPs, highlighting their potential as natural antioxidants. This study is the first to link apricot kernel peptides to PS-MPs-induced endothelial protection, providing novel insights into combating microplastic-related cardiovascular risks.</p><p><strong>Conclusion: </strong>AKPE exerts potent protective effects against oxidative and inflammatory injury in HAECs caused by PS-MPs. These effects are mediated by its constituent bioactive oligopeptides, which concurrently regulate the NLRP3 inflammasome and Wnt/β-catenin signaling pathways. Our findings highlight AKPE's potential as a promising natural therapeutic agent for alleviating vascular endothelial damage associated with microplastic exposure.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"337-348"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Peptidomics: A New Dimension in Microbiome Research.","authors":"Kai Hilpert","doi":"10.2174/0109298665436241260327111926","DOIUrl":"10.2174/0109298665436241260327111926","url":null,"abstract":"<p><p>The human gut microbiome is now recognised as a major determinant of health, with roles extending beyond digestion to influence neurodegeneration, metabolism, immunity, and pharmacological responses. Clinical studies link microbial imbalances to Alzheimer's disease, Parkinson's disease, depression, and cardiovascular disorders, yet the underlying mechanisms remain only partly understood. Methodological advances have progressively deepened our insight. DNA-based sequencing (metagenomics) catalogues microbial genes but reveals only potential functions. RNA-based sequencing (metatranscriptomics) highlights active gene expression, but instability of transcripts and poor correlation with protein activity limit its predictive value. Metabolomics measures small-molecule end products, providing direct evidence of microbial biochemistry and identifying disease-linked metabolites such as urolithin A, trimethylamine N-oxide, and equol. These approaches together have transformed microbiome science, but they remain incomplete. A critical and underutilised dimension is peptidomics: the systematic analysis of endogenous peptides in the gut and circulation. Enabled by peptide-enriching, protease-inhibiting workflows and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), peptidomics directly captures unstable signaling peptides and proteolytic fragments that are often invisible to conventional proteomics. Coupled with emerging gut-specific peptide databases, such as MetaPep, and Artificial Intelligence (AI) assisted de novo sequencing and spectral prediction for non-human peptides, this provides a concrete technical route to reading out the functional peptide layer of the microbiome. Peptidomics can capture functional signals of host-microbiome interaction, reveal context-specific biomarkers, and provide mechanistic insight into disease. Recent studies demonstrate that peptide-level resolution uncovers microbial contributions to gut inflammation, modulates the gut-brain axis, and enables peptide-based disease stratification in conditions such as inflammatory bowel disease. However, despite these promising examples, peptidomics remains largely absent from mainstream microbiome research. Integrating peptidomics with existing genomic, transcriptomic, and metabolomic approaches will generate a more complete and functional picture of the microbiome. This shift will accelerate biomarker discovery, refine diagnostics, and expand the search for peptide-based therapeutics, positioning peptidomics as an essential next step in microbiome science.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"488-496"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}