The protein journal最新文献

{"title":"Unlocking the Therapeutic Potential of Cyclic Peptide-Based Nanocarriers for Enhanced Colon Cancer Treatment.","authors":"Vedhapriya Souresh, M Srikayalsamyukktha, M Harini, Yudhesh Saravanan, Rupachandra Saravanakumar","doi":"10.1007/s10930-025-10289-2","DOIUrl":"https://doi.org/10.1007/s10930-025-10289-2","url":null,"abstract":"<p><p>Cyclic peptides have emerged as therapeutic agents for colon cancer due to their structural stability, enhanced bioavailability, and high target specificity. Natural cyclic peptides derived from plant, marine, and microbial sources exhibit potent anticancer properties. Advancements in nanotechnology have facilitated using cyclic peptide-based nanocarriers to improve drug delivery, enhance tumor penetration, and minimize adverse effects. Nanocarriers including liposomes, niosomes, nanosponges, and nanopolymers provide a revolutionary approach by facilitating localized distribution, enhanced stability, and controlled release of cyclic peptides. This strategy improves pharmacokinetics and lowers systemic toxicity to overcome the limitations of conventional treatments. Recent developments in cyclic peptide-based nanotechnology demonstrate the synergy between cyclic peptides and nanocarriers in overcoming drug resistance in colon cancer. This review provides a comprehensive overview of the sources, mechanisms of action, and therapeutic applications of cyclic peptides in colon cancer treatment. It further explores the role of cyclic peptide-functionalized nanocarriers in overcoming drug resistance and improving drug delivery.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of Serum Samples in Ovulatory Polycystic Ovary Syndrome and Construction of a Protein Interaction Pathway.","authors":"Ahmad Fazilat, Keivan Majidzadeh-A, Kambiz Gilany, Fatemeh Mortazavi Moghadam, Mohammad Valilo, Saima Wajid","doi":"10.1007/s10930-025-10295-4","DOIUrl":"https://doi.org/10.1007/s10930-025-10295-4","url":null,"abstract":"<p><p>As a heterogeneous multifactorial disorder, PCOS still has a misty etiology. Its underlying pathophysiological causes can be further elucidated by proteomic analyses and molecular network analysis to understand the interaction pathways involved in the PCOS-associated perturbations. We conducted a proteomic study on ovulatory PCOS serum samples using nano-LCMS/MS technique. Then, we analysed the proteomic profiles of substantially dysregulated proteins by projecting them onto protein interaction mapping and molecular network analysis software tools Gene Mania and STRING. We further investigated the involvement of the affected proteins in different PCOS-associated disorders and classified them through a review of the literature along with functional annotation software tools DAVID and Panther. We found a total of 228 proteins in serum; 109 were found in both ovulatory PCOS and controls, and 42 of those showed a difference of ≥twofold (19 higher in ovulatory PCOS and 23 lower). Among them, 35 proteins exhibited an association with the pathophysiological mechanisms underlying the manifestation of ovulatory PCOS manifestation and their correlations with PCOS-concurrent disorders were revealed. There were also 87 proteins that were only found in ovulatory PCOS and 32 that were only found in controls. We further highlighted significant functional hub molecules within protein interaction networks. Our findings indicated that the ovulatory PCOS involves a wide range of functional molecule derangements, which trigger aberrant biological responses and molecular interactions leading to the emergence of complications associated with ovulatory PCOS. Further omics studies are required to explain the different physiological mechanisms of the functional molecules contributing to the pathogenicity of this heterogeneous syndrome.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic In-Silico Insights into the Anti-quorum Sensing Potential of Coumaric Acid and Syringic Acid in Serratia marcescens with Invitro Analysis.","authors":"Pooja Pandey, Bipin R Shekhar, Dhanjit K Das, Sirisha L Vavilala","doi":"10.1007/s10930-025-10292-7","DOIUrl":"https://doi.org/10.1007/s10930-025-10292-7","url":null,"abstract":"<p><p>Antibiotic resistance presents a major global health threat, especially with ESKAPE pathogens like Serratia marcescens, which exhibit resistance to all known antibiotics. Quorum sensing (QS) is key to its virulence and resistance, emphasizing the need for novel natural antimicrobial agents. This study investigates two plant-derived phenolic compounds, coumaric acid and syringic acid, targeting QS proteins of S. marcescens using in silico molecular docking, molecular dynamics simulations, and in vitro biochemical assays. Validated homology models of eight QS-associated proteins-BsmA, FimA, FimC, FlhD, LuxS, PigP, RsmA, and RssB-were employed for molecular docking studies, ADME (absorption, distribution, metabolism, and excretion) profiling, and 100-ns molecular dynamics (MD) simulations to evaluate ligand-binding stability. Coumaric acid displayed more desirable physicochemical properties (logP 1.79; TPSA 57.53 Ų) compared to syringic acid (logP 1.04; TPSA 75.99 Ų). Binding energy calculations indicated a stronger affinity of coumaric acid for six of the proteins, with the LuxS-coumaric acid complex showing the most significant interaction (ΔGbind - 21.74 ± 3.01 kcal/mol). Analysis of the MD trajectory revealed that coumaric acid enhanced protein stability, as shown by reductions in RMSF (root mean square fluctuation), a more compact Rg (radius of gyration), decreased SASA (solvent-accessible surface area), alterations in the Dictionary of secondary structure of protein (DSSP), and consistent hydrogen bonding. Conversely, syringic acid induced increased conformational flexibility and destabilized alpha-helices and beta-sheets in specific proteins. Principal component analysis (PCA) confirmed tighter conformational clustering in coumaric acid complexes, consistent with improved stabilization. Furthermore, antibacterial assays demonstrated strong inhibitory effects, with MIC values of 700 µg/mL for coumaric acid and 1000 µg/mL for syringic acid. Coumaric acid displayed a bactericidal effect, whereas syringic acid was bacteriostatic. Additionally, time-kill assays revealed a dose-dependent reduction in bacterial growth over 48 h following treatment with varying concentrations of these phenolic acids . Interestingly, qPCR analysis of QS-specific gene expression showed significant downregulation of key QS-regulated genes in response to both compounds, highlighting their potential as quorum-sensing inhibitors and supporting their development as alternative antimicrobial agents against antibiotic-resistant S. marcescens.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Phosphorylation Landscape of Anthrax Toxin Receptor 1: Mechanisms and Functional Insights Through Phosphoproteomic Data Integration.","authors":"Ayadathil Sujina, Amal Fahma, Suhail Subair, Leona D'cunha, Athira Perunelly Gopalakrishnan, Samseera Ummar, Prathik Basthikoppa Shivamurthy, Poornima Ramesh, Rajesh Raju","doi":"10.1007/s10930-025-10293-6","DOIUrl":"https://doi.org/10.1007/s10930-025-10293-6","url":null,"abstract":"<p><p>Anthrax Toxin Receptor 1 (ANTXR1) is a transmembrane protein involved in various biological processes, including angiogenesis, cell adhesion, and migration. As a receptor for Bacillus anthracis toxins and the oncolytic Seneca Valley virus, ANTXR1 plays pivotal roles in extracellular matrix interactions, actin cytoskeleton organization, and tumor progression. Despite its relevance in cancer biology, ANTXR1 remains understudied from a phosphoproteomics perspective. In this study, we report the phosphoproteomic landscape of the ANTXR1 protein through a unique data integration strategy from a mass spectrometry-based phosphoproteomics perspective. Through robust statistical analyses, conserved phosphorylation events of ANTXR1 across diverse experimental conditions were linked to its upstream kinases and binary interactors to deduce specific events modulated through ANTXR1 phosphorylation. This computational analysis of curated datasets identified conserved ANTXR1 phosphorylation events along with similar and oppositely co-regulated phosphorylation events of adjunct proteins, revealing extensive regulatory networks of ANTXR1. Our findings provide phosphorylation-dependent interaction between ANTXR1 and FLNA and their upstream kinases and phosphobinding motifs, emphasizing their collective role in cell migration. Overall, the study enhances the integrative analysis of mass spectrometry-based phosphoproteomics data through bioinformatics and statistical approaches.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Wheat Leaf Urease for a Sustainable Approach: Purification, Kinetics, and Thermal Stability Characterization.","authors":"Surbhi Sahewalla, Sonam Sihag, Anil Duhan, Vinod Saharan, Ajay Pal","doi":"10.1007/s10930-025-10291-8","DOIUrl":"https://doi.org/10.1007/s10930-025-10291-8","url":null,"abstract":"<p><p>The urease enzyme has an inevitable application in cereal crops, particularly in response to foliar urea application. A holistic and novel approach was employed in the present work with the aim to purify and characterize the wheat leaf urease. This will help in exploring and enhancing its activity in assimilation of foliar urea application and a move towards sustainability. Wheat urease was purified to electrophoretic homogeneity with a 41.98 fold purification and 36.3% recovery. The molecular weight of the native enzyme was found to be ~ 290 kDa by Gel Filtration Chromatography (GFC), and a single band in Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) of ~ 103 kDa deduced its homotrimeric nature. The enzyme had a K_m of 1.0 mM, V_max of 63.25 units mL^-1, turnover number of 30.26 min^-1, and a specificity constant of 504.33 M^-1 sec^-1. Further, the optimum pH was 7.5 with 40 °C optimum temperature. The E_a of the purified urease was 61.36 kJ mol^-1, with the E_d as 104.3 kJ mol^-1. The half-life and D-value decreased with an increase in temperature owing to the rapid loss of its catalytic activity. The z-value was calculated as 44.6 °C. The thermodynamic study revealed the interplay between ΔH, ΔG and ΔS during enzyme deactivation. Histidine was found to be present at the active site and Nickel enhanced the urease activity, whereas copper displayed an inhibitory effect. Hence, this study of wheat urease offers novel insights into an enzyme that has remained largely unexplored despite its inevitable importance in cereal crops. The measures for enhancing its activity in vivo can also be abstracted from this study.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Verification Process of a Structure-Altering Peptide as a Microtubule Allosteric Polypeptide Against Cancer.","authors":"Zhan Shi","doi":"10.1007/s10930-025-10290-9","DOIUrl":"https://doi.org/10.1007/s10930-025-10290-9","url":null,"abstract":"<p><p>The aim of this study was to design a novel structure-altering polypeptide (SAP) as an anti-microtubule against tumor cells. This series of SAP XA1-XA17 was synthesized by manual solid-phase synthesis and verified by high-performance liquid chromatography (HPLC) and mass spectrometry. Polypeptides were used in three normal cell lines and four tumor cell lines. The optimal polypeptide was selected. Molecular docking of the above optimal polypeptide with tubulin was performed. Tubulin polymerization experiment was performed to investigate effect of optimized peptide to tubulin polymerization. The effect of optimized peptide to cancer in vivo was tested in A549 xenograft tumor mice model. The results of mass spectrometry revealed that the molecular weights of the SAP XA1-XA17 samples were relatively consistent with the theoretical values, whereas the purities of the SAP XA1-XA17 series polypeptide samples were greater than 92.00%. Among the SAP XA1-17 polypeptides, the cell viability kit-8 (CCK-8) assay demonstrated that the XA5 polypeptide was nearly nontoxic to three normal cell lines and had excellent antitumor effects on four cancer cell lines. Molecular docking demonstrated that the polypeptide XA5 preferred tubulin. The docking energies are less than - 5 kcal/mol, verifying the excellent performance of the selected XA5 polypeptide. Tubulin polymerization experiment showed XA5 inhibited tubulin polymerization. In animal study, XA5 administration decreased A549 xenograft tumor weight. The XA5 polypeptide is an effective anti-microtubule drug.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Recombinant Stonustoxin Alpha Subunit and Preparation of polyclonal antiserum for Stonustoxin Neutralization Studies.","authors":"Amir Sajjad Hojjati-Razgi, Shahram Nazarian, Hossein Samiei-Abianeh, Amir Vazirizadeh, Emad Kordbacheh, Seyed Mojtaba Aghaie","doi":"10.1007/s10930-024-10203-2","DOIUrl":"10.1007/s10930-024-10203-2","url":null,"abstract":"<p><p>Stonustoxin (SNTX) is a lethal protein found in stonefish venom, responsible for many of the symptoms associated with stonefish envenomation. To counter stonefish venom challenges, antivenom is a well-established and effective solution. In this study, we aimed to produce the recombinant alpha subunit protein of Stonustoxin from Synanceia horrida and prepare antibodies against it The SNTXα gene sequence was optimized for E. coli BL21 (DE3) expression and cloned into the pET17b vector. Following purification, the recombinant protein was subcutaneously injected into rabbits, and antibodies were extracted from rabbit´s serum using a G protein column As a result of codon optimization, the codon adaptation index for the SNTXα cassette increased to 0.94. SDS-PAGE analysis validated the expression of SNTXα, with a band observed at 73.5 kDa with a yield of 60 mg/l. ELISA results demonstrated rabbits antibody titers were detectable up to a 1:256,000 dilution. The isolated antibody from rabbit´s serum exhibited a concentration of 1.5 mg/ml, and its sensitivity allowed the detection of a minimum protein concentration of 9.7 ng. In the neutralization assay the purified antibody against SNTXα protected mice challenged with 2 LD50. In conclusion, our study successfully expressed the alpha subunit of Stonustoxin in a prokaryotic host, enabling the production of antibodies for potential use in developing stonefish antivenom.</p>","PeriodicalId":94249,"journal":{"name":"The protein journal","volume":" ","pages":"627-638"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}