Protein and Peptide Letters最新文献

{"title":"Unlocking the Keratinolytic Potential of <i>Brevibacillus agri</i> Derived Keratinase: A Molecular Characterization Study.","authors":"Hira Batool, Beenish Maqsood, Hira Muzzamal, Hamama Islam Butt, Roquyya Gul, Farooq Latif, Mahjabeen Saleem","doi":"10.2174/0109298665378063250628211031","DOIUrl":"10.2174/0109298665378063250628211031","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Keratinases have an established role in degrading highly stable and insoluble fibers of keratin proteins, which are otherwise difficult to be hydrolyzed by conventional proteases. Keratinases find promising application in degrading poultry waste to valuable products. Moreover, their role in cosmetics, detergents, agriculture and the leather industry is well recognized.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;In this study, the keratinase gene from locally isolated &lt;i&gt;Brevibacillus agri&lt;/i&gt; bacteria was cloned and expressed in &lt;i&gt;Escherichia coli&lt;/i&gt;, and some of its potential applications were explored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;1300 bp amplified gene from &lt;i&gt;Brevibacillus agri&lt;/i&gt; was cloned into E. coli DH5α competent cells using pTZ57R/T vector. After blue-white screening, the positive clone was confirmed by colony PCR and restriction analysis. Purified keratinase gene KerH from recombinant pTZR/KerH plasmid was ligated into pET-28a (+) and transferred into competent cells of E. coli DH5α. Following confirmation through colony PCR, and restriction analysis, recombinant plasmid (pET-28a/Ker) from the positive clone was transferred into competent E. coli BL21 cells. The transformed cells were then cultured for up to 8 hours after induction with 0.8 mM IPTG and lysed by sonication. The resulting recombinant keratinase (KerH) was purified by heat treatment and Ni-affinity column and characterized.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The blast analysis and homologous sequences in the NCBI database established a close link to Brevibacillus agri. The highest expression from transformed E. coli BL21 was achieved with 0.8 mM IPTG following 6 hours of induction. The resulting recombinant keratinase (KerH), purified by Ni-affinity chromatography, possessed 283 U/mg specific activity and displayed ~45 kDa band on SDS-PAGE and zymogram. Secondary structure analysis and active site prediction was performed computationally. Considering the extensive applications of keratinase, KerH was found to be useful in dehairing animal skin surfaces without any damage. The encapsulated KerH possessed improved stability and better compatibility with commercial detergents. It efficiently removed blood, turmeric, strawberry, and egg yolk stains from the fabric. Furthermore, KerH significantly degraded the poultry feathers and provided a protein hydrolysate that helped in converting damaged, dull and curly hair into healthier, shiny and straightened hair.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;These key findings highlight that KerH is a robust keratinase with significant potential as an environmental-friendly alternative to the prevailing harsh chemical treatments in various industries. Encapsulation enhanced its suitability by improving its stability and shelf-life. Its broader substrate specificity, stability and application in detergents and cosmetics underline its commercial importance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The recombinant KerH fro","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"525-538"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691292","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":"Nickel Binding to the c-Src SH3 Domain Facilitates Crystallization.","authors":"Xander Calicdan, Oriana S Fisher, Byung Hak Ha, Titus J Boggon, Amy L Stiegler","doi":"10.2174/0109298665417324250929120040","DOIUrl":"10.2174/0109298665417324250929120040","url":null,"abstract":"<p><strong>Introduction: </strong>Numerous X-ray crystal structures of the c-Src SH3 domain have provided a large sampling of atomic-level information for this important signaling domain. Multiple crystal forms have been reported, with variable crystal lattice contacts and chemical crystallization conditions.</p><p><strong>Materials and methods: </strong>We crystallized the c-Src SH3 domain in a crystallization buffer containing NiCl₂.</p><p><strong>Results: </strong>A unique crystal structure of the Src SH3 domain in the trigonal space group H32 is determined to 1.45 Å resolution. Crystal packing and anomalous scattering reveal that this crystal form is mediated by two ordered nickel ions provided by the crystallization buffer. Nickel coordination occurs in a 2:2 stoichiometry, which dimerizes two SH3 domain monomers across a pseudo-twofold rotation axis and involves the native N-terminal c-Src SH3 amino acid sequence, a surface-exposed histidine residue, and ordered water molecules.</p><p><strong>Discussion: </strong>This study provides an example of metal-mediated crystallization and metal binding by N-terminal protein residues, contrasting with the Amino-Terminal Copper and Nickel Binding (ATCUN) motif.</p><p><strong>Conclusion: </strong>Alternative avenues help widen the potential for future crystallography-based studies of the c-Src SH3 domain.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"679-692"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12582252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293384","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":"F18 Promiscuous Epitope of Acr1 Protein of <i>Mycobacterium tuberculosis</i> Induces the Secretion of IL-10 and Tregs but Not IL-6.","authors":"Taruna Lamba, Shivank Prajapati, Arnab Chowdhury, Anupam Bandyopadhyay, Javed N Agrewala","doi":"10.2174/0109298665398349250728195645","DOIUrl":"10.2174/0109298665398349250728195645","url":null,"abstract":"<p><strong>Introduction: </strong><i>Mycobacterium tuberculosis</i> (Mtb) is a Gram-positive bacterium that causes tuberculosis (TB). It remains viable for extended periods within host macrophages by entering a dormant state. Alpha crystallin 1 (Acr1) is a 16 kDa protein of Mtb and is reported to be highly upregulated in latent TB. Acr1 suppresses the host's immune system by impairing the differentiation and maturation of dendritic cells and macrophages. We hypothesize that Mtb judiciously utilizes its Acr1 protein to paralyse the immune system of the host by inducing the release of IL-10 and generating an immunosuppressive environment.</p><p><strong>Methods: </strong>We employed <i>in silico</i> tools to identify highly promiscuous, IL-10-inducing and IL-6- non-inducing epitopes of Mtb. Moreover, the selected epitope was synthesized and tested for its suppressive activity and generation of Tregs.</p><p><strong>Results: </strong>We identified the presence of a specific epitope in Acr1 (F18) that is responsible for bolstering the release of IL-10 and Tregs through <i>in silico</i> tools and verified the activity by in vitro assays. In hPBMCs, the F18 epitope could suppress the proliferation of CD4 T cells stimulated with PHA and expand the pool of Tregs in a dose-dependent manner.</p><p><strong>Discussion: </strong>The F18 epitope from Mtb's Acr1 protein promotes IL-10 and Treg responses without triggering pro-inflammatory IL-6, suggesting its probable immunoregulatory role. While it holds potential for treating autoimmune diseases, its impact on infection in tuberculosis should be further investigated.</p><p><strong>Conclusion: </strong>Our findings suggest that the F18 epitope induces IL-10 production and Treg differentiation while inhibiting CD4+ T cell proliferation and IL-6 secretion, thereby promoting an immunosuppressive environment. Furthermore, this study highlights the possible role of Acr1 and its immunosuppressive epitope F18 as therapeutic agents for inducing suppressive Tregs, which may help in the management of autoimmune diseases.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"610-619"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837483","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":"Effect of Adipokinetic Hormone on Learning-Memory in a Scopolamine-Induced Alzheimer's Model in Mice.","authors":"Emre Uyar, Sibel Kokturk, Mohammed Omer Khalid Mohammed, Pınar Cobanturk, Nouralhuda A Z Abuqaoud, Furuzan Akar, Guner Ulak, Faruk Erden, Oguz Mutlu","doi":"10.2174/0109298665380324250602054823","DOIUrl":"10.2174/0109298665380324250602054823","url":null,"abstract":"<p><strong>Introduction: </strong>Neurosecretory cells of insects synthesize Adipokinetic Hormone (AKH). Previous studies indicated that AKH improves memory functions. This study aimed to explore the effects of AKH on learning and memory in an Alzheimer's disease model.</p><p><strong>Methods: </strong>Morris Water Maze (MWM), Passive Avoidance (PA), and Modified Elevated Plus Maze (mEPM) tests were conducted in BALB/c mice. Initially, each group consisted of 8 to 9 animals; in total, 120 animals were used in this study. The groups included control, Ani-AKH (1 and 2 mg/kg), Lia-AKH (1 and 2 mg/kg), Pht-HrTH (1 and 2 mg/kg), Scopolamine (1 mg/kg), and Scopolamine combinations. Hormones were given for 6 days in the MWM test to evaluate learning and memory before the second trial in the PA test for memory assessment and after the first trial in the mEPM test to examine consolidation.</p><p><strong>Results: </strong>In the MWM test, Ani-AKH and Pht-HrTH reduced escape latency compared to the scopolamine group (p<0.05). During the probe trial, Ani-AKH increased time in the escape platform quadrant (p<0.5) and reversed scopolamine's effects (p<0.001). Lia-AKH and Pht-HrTh did not affect time in the quadrant but reversed scopolamine's effects (p<0.01). In the PA test, Ani- AKH reversed scopolamine's effects (p<0.5), while Lia-AKH did so in the mEPM test (p<0.01). The control group showed strong muscarinic receptor staining, while the scopolamine group did not. Ani-AKH and Lia-AKH showed moderate to strong receptor staining, indicating partial restoration.</p><p><strong>Discussion: </strong>AKH and its analogs may enhance memory function by modulating cholinergic pathways, particularly through the partial restoration of muscarinic receptor activity. These results underscore their potential as investigational therapeutics for neurodegenerative disorders characterized by cognitive decline.</p><p><strong>Conclusion: </strong>Our study indicates that AKH may help reduce memory impairments, though the effects depend on the specific assessment methods used in the tests.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"423-436"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529354","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":"Engineered Bacteriophages: Advances in Phage Genome Redesign Strategies for Therapeutic and Environmental Applications.","authors":"Marzieh Rezaei, Amir Jalali, Dheyaa Hussein Sadah Al-Azzawi","doi":"10.2174/0109298665372719250616085616","DOIUrl":"10.2174/0109298665372719250616085616","url":null,"abstract":"<p><p>Bacteriophages, or phages, have emerged as powerful platforms in synthetic biology, offering innovative solutions for therapeutic and environmental challenges through advanced genome redesign strategies. This review explores a wide range of phage engineering techniques, including CRISPR (clustered regularly-interspaced short palindromic repeats)-Cas systems, phage display, random and site-directed mutagenesis, retrons, and rebooting approaches, highlighting their potential to create phages with tailored functionalities. CRISPR-Cas systems enable precise genome editing, allowing the development of phages with expanded host ranges, biofilm degradation capabilities, and targeted antimicrobial activity. Phage display facilitates the presentation of peptides on phage surfaces, enabling applications in targeted drug delivery, tumor imaging, and bioremediation. Beyond these, techniques like retron-mediated recombination and homologous recombination offer additional avenues for precise phage genome modification. In the therapeutic realm, engineered phages show promise in combating drug-resistant infections, modulating the microbiome, and delivering targeted therapies for cancer and other diseases. Environmentally, phage-based strategies, such as the use of phage-displayed metal-binding peptides, provide innovative solutions for bioremediation and reducing exposure to toxic heavy metals. This review also addresses challenges, such as phage resistance, immune responses, and the limitations of current engineering methods, while exploring future directions, including the development of improved CRISPR systems, phage-based biosensors, and high-throughput screening platforms. By integrating cutting-edge genome redesign strategies with diverse applications, this review underscores the transformative potential of engineered bacteriophages in addressing global healthcare and environmental sustainability challenges.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"387-401"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560878","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":"Cell-Free Expression of HPV16 Minor Capsid Protein L2 and Its Interaction with S100A10.","authors":"Wenqi Jiang, Lian Wu, Xiangchun Shen, Qingshan Bill Fu","doi":"10.2174/0109298665390494250513110604","DOIUrl":"10.2174/0109298665390494250513110604","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus type 16 (HPV16) is implicated in various malignancies. The virus enters host cells through endocytosis, during which the minor capsid protein L2 interacts with the S100A10 subunit of the annexin A2 heterotetramer (A2t) on the host cell membrane. This interaction is critical for facilitating HPV entry and subsequent infection of human cells. Therefore, examining the interaction between the L2 protein and S100A10 is crucial for advancing our understanding of the mechanisms by which HPV16 infiltrates cells.</p><p><strong>Objective: </strong>The cell-free expression (CFE) system was investigated for L2 purification. The structure of L2 was characterized and its interaction with S100A10 was explored.</p><p><strong>Methods: </strong>The L2 protein was expressed using a CFE expression system, and its expression was verified via Western blotting. L2 was further purified through size-exclusion chromatography (SEC), and its structural features were preliminarily assessed using transmission electron microscopy (TEM) and circular dichroism (CD) spectroscopy. Additionally, surface plasmon resonance (SPR) was employed to analyze the interaction between L2 and S100A10.</p><p><strong>Results: </strong>Western blotting confirmed the successful expression of L2. TEM and CD provided preliminary structural observations of L2, and SPR measurements yielded precise kinetic parameters for the interaction between L2 and S100A10.</p><p><strong>Conclusion: </strong>In this study, we successfully expressed the HPV16 L2 protein using a cell-free protein expression system. Preliminary structural analysis using TEM and CD revealed key structural features of L2. Furthermore, SPR analysis provided detailed kinetic parameters for its interaction with S100A10. These findings provide more details on understanding L2's structural features, with broader implications for antipathogen studies.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"376-386"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142985","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":"Optimized Strategy for Expression, On-Column Refolding, and Purification of NEDD8 Protein.","authors":"Shalu Yadav, Neeraj Kumar Fauzdar, Yashwant Kumar Yadav, Gajendra Singh","doi":"10.2174/0109298665422034251021111813","DOIUrl":"10.2174/0109298665422034251021111813","url":null,"abstract":"<p><strong>Introduction: </strong>Ubiquitin and the Ubls family are known for their high solubility and excellent expression profiles in recombinant systems. In contrast, Neural Precursor Cell Expressed, Developmentally Down-Regulated 8 (NEDD8) is a ubiquitin-like modifier that shares more than 60% sequence identity with ubiquitin and exhibits a similar structural fold. NEDD8 primarily functions by modifying the cullin subunits of cullin-RING E3 ligases, thereby playing a critical role in regulating the cell cycle, embryonic development, and DNA repair processes, particularly by localizing to sites of DNA damage. Despite its structural and functional similarity to highly soluble ubiquitin family proteins, recombinant NEDD8 is predominantly expressed in inclusion bodies, making its purification challenging.</p><p><strong>Methods: </strong>Traditional refolding and purification strategies using 6M urea have proven inefficientin recovering properly folded and functional protein. In this study, we present a streamlined, high- - yield method for purifying NEDD8 based on on-column refolding using a 6xHis tag in combina-- tion with nickel-affinity chromatography, followed by size exclusion chromatography for further purification. We applied an on-column refolding method for NEDD8, eliminating dialysis-associated losses and yielding well-folded protein. The approach is effective for small proteins but limited by size, hydrophobicity, and charge-related aggregation risks. Broader applicability requires case-specific optimization to ensure correct folding and structural fidelity across diverse proteins.</p><p><strong>Results: </strong>The structural integrity and correct folding of the purified NEDD8 were confirmed through both nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy, validating the effectiveness of the method for producing biologically relevant, properly folded protein.</p><p><strong>Conclusion: </strong>Our results demonstrate that this on-column refolding approach significantly improves the yield and refolding efficiency of NEDD8 compared to previous urea-based methods.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"803-810"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053361","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":"Mevalonate Metabolic Reprogramming Drives Cisplatin Resistance in Bladder Cancer: Mechanisms and Therapeutic Targeting.","authors":"Qixiang Fang, Chengyu You, Xi Xiao, Yang Liu, Weiguang Yang, Qingchao Li, Liangliang Qing, Zhilong Dong","doi":"10.2174/0109298665403178250806111943","DOIUrl":"10.2174/0109298665403178250806111943","url":null,"abstract":"<p><strong>Introduction: </strong>Dysregulation of mevalonate metabolism is a hallmark of tumorigenesis and therapy resistance across malignancies, though its role in bladder cancer remains unclear. This study aimed to elucidate its impact on prognosis and cisplatin chemosensitivity in bladder cancer.</p><p><strong>Methods: </strong>Transcriptomic data and clinical information of bladder cancer patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Non-negative matrix factorization (NMF) was used to cluster mevalonate metabolism-related genes into distinct metabolic subtypes (C1 and C2). Associations between mevalonate metabolism, clinical characteristics, immune infiltration, and cisplatin resistance were analyzed using Gene Set Variation Analysis (GSVA), Kaplan-Meier survival analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), and in vitro experiments.</p><p><strong>Results: </strong>NMF clustering classified bladder cancer patients into two metabolic subtypes (C1/C2). The C1, characterized by higher mevalonate metabolism (MVAscore), was associated with a poorer prognosis, shorter overall survival (OS), and higher T-stage and pathological grades. Immune analysis showed lower immune cell infiltration in C1. Immune infiltration analysis revealed significantly lower immune infiltration levels in the C1. Further analysis revealed a positive correlation between mevalonate metabolism and platinum resistance, with a notable increase in mevalonate metabolism observed in cisplatin-resistant bladder cancer cells. In vitro, simvastatin inhibited the proliferation of bladder cancer cells and enhanced their sensitivity to cisplatin.</p><p><strong>Discussion: </strong>Mevalonate metabolism drives BCa heterogeneity and chemoresistance while suppressing anti-tumor immunity. Its dysregulation serves as both a prognostic biomarker and a target for therapeutic intervention.</p><p><strong>Conclusion: </strong>Mevalonate metabolism contributes to cisplatin resistance in bladder cancer and represents a potential therapeutic target. Simvastatin targeting this pathway enhances the efficacy of cisplatin, providing a novel personalized chemotherapy strategy.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"597-609"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016019","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":"Precision Enzyme: Targeted Drug Discovery in Neurodegenerative Disorders.","authors":"Sampriti Paul, Prashant Tiwari, Sonal Dubey","doi":"10.2174/0109298665391103250825102319","DOIUrl":"10.2174/0109298665391103250825102319","url":null,"abstract":"<p><strong>Introduction: </strong>Neurodegenerative disorders such as Alzheimer's, Parkinson's, and ALS are characterized by progressive neuronal dysfunction with limited therapeutic options. Recent advances in molecular biology and drug development have highlighted the therapeutic promise of precision enzyme targeting, offering novel strategies for disease modulation and symptom management.</p><p><strong>Methods: </strong>A comprehensive literature review spanning recent/current was conducted using PubMed, Scopus, and ScienceDirect. Studies focusing on enzyme-based targets, high-throughput screening, and molecular docking in neurodegeneration were included. Thematic synthesis was employed to categorize findings based on enzyme class, disease relevance, and therapeutic outcomes.</p><p><strong>Results: </strong>Key enzyme families such as kinases, proteases, and oxidoreductases were identified as pivotal modulators in disease progression. Emerging enzyme-targeted compounds demonstrated enhanced bioavailability, blood-brain barrier permeability, and disease-specific efficacy. Novel screening platforms and computational modeling enabled the precise selection of inhibitors, significantly improving the therapeutic index and reducing off-target effects.</p><p><strong>Discussion: </strong>Targeting enzymes implicated in neuroinflammation, oxidative stress, and protein misfolding has shown disease-modifying potential. Integrating precision drug discovery tools, such as AI-assisted modeling and enzyme kinetics, supports rational drug design. However, translational challenges persist due to variability in enzyme expression and disease heterogeneity.</p><p><strong>Conclusion: </strong>Future research should focus on refining enzyme inhibitors and integrating biomarkers to facilitate personalized treatment strategies for neurodegenerative disorders. As the understanding of enzymatic roles in neurodegeneration deepens, precision enzyme-targeted drug discovery holds significant promise in transforming neurotherapeutic approaches.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"539-556"},"PeriodicalIF":1.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001376","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":"Amphibian-Derived Antimicrobial Peptides: Essential Components of Innate Immunity and Potential Leads for New Antibiotic Development.","authors":"Ebru Tanriverdi O","doi":"10.2174/0109298665356946241218103145","DOIUrl":"10.2174/0109298665356946241218103145","url":null,"abstract":"<p><p>Like other vertebrates, amphibians possess innate and adaptive immune systems. At the center of the adaptive immune system is the Major Histocompatibility Complex. The important molecules of innate immunity are antimicrobial peptides (AMPs). These peptides are secreted by granular glands in the skin and protect the animal against microorganisms entering its body through the skin. AMPs offer an effective and rapid defense against pathogenic microorganisms and have cationic and amphiphilic structures. These peptides are small gene-encoded molecules of 8-50 amino acid residues synthesized by ribosomes. These small molecules typically exhibit activity against bacteria, viruses, fungi, and even cancer cells. It is known that today's amphibian AMPs originated from a common precursor gene 150 million years ago and that the origin of these peptides is preprodermaseptins. Today, antibiotic resistance has occurred due to the incorrect use of antibiotics. Traditional antibiotics are becoming increasingly inadequate. AMPs are considered promising candidates for the development of new-generation antibiotics. Therefore, new antibiotic discoveries are needed. AMPs are suitable molecules for new-generation antibiotics that are both fast and have different killing mechanisms. One of the biggest problems in the clinical applications of AMPs is their poor stability. AMPs generally have limited tropical applications because they are sensitive to protease degradation. Coating these peptides with nanomaterials to make them more stable can solve this problem.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"97-110"},"PeriodicalIF":1.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953978","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}