Current pharmaceutical biotechnology最新文献

{"title":"A Roadmap Towards the Identification and Validation of Conserved T Cell Epitope Regions in Viral Pathogen Families with Pandemic Potential.","authors":"Alba Grifoni, John Sidney, Daniela Weiskopf, Richard H Scheuermann, Alessandro Sette","doi":"10.2174/0113892010349200241204062202","DOIUrl":"https://doi.org/10.2174/0113892010349200241204062202","url":null,"abstract":"<p><p>The SARS-CoV-2 pandemic has highlighted the need for society, as a whole, to be prepared against potential pandemics caused by a variety of different viral families of concern. Here, we describe a roadmap towards the identification and validation of conserved T cell epitope regions from Viral Families of Pandemic Potential (VFPP). For each viral family, we select a prototype virus, the sequence of which could be utilized in epitope identification screens. Examples of viral families considered and their respective prototypes (species/ subspecies) are Coronaviridae (Severe Acute Respiratory Syndrome-related Coronavirus/ SARS-CoV-2), Flaviviridae (Dengue virus/DENV2), Togaviridae (Chikungunya virus/ CHIKV), Paramyixoviridae (Morbillivirus/measles), Arenaviridae (Mammarenavirus/ Lassa), and Picornaviridae (Enterovirus C/poliovirus). The peptide sequences encoded in each prototype virus are then analyzed to determine their conservation across different viral taxonomic groups and viral variants derived from each of the VFPP. We outline available methodologies for epitope discovery based on panels of overlapping peptides and bioinformatics- based predictions of HLA-peptide binding, along with high-throughput in vitro assays, with emphasis on addressing coverage of the general worldwide population. Validation can be achieved by a variety of methodologies, including determining HLA restriction and recognition in samples from volunteers convalescent from previous infections or immunized with approved or experimental vaccines, and immunophenotyping of responding T cells. The capacity of these regions to induce crossreactive T cell responses can be tested experimentally with homologous peptides derived from the various viral species of interest. Importantly, they could be considered as a component of pan-viral family vaccines. Conversely, immunogenic regions that are highly specific to a given virus could be of interest for diagnostic applications.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Skin Whitening Creams: Cosmetovigilance.\"","authors":"Saloni Agarwal, Mohd Mazhar, Hiranmoy Saha, Simra Khan, Mohammad Ibrahim, Charu Chhabra","doi":"10.2174/0113892010323719241205045837","DOIUrl":"https://doi.org/10.2174/0113892010323719241205045837","url":null,"abstract":"<p><p>Cosmeceutical products such as skin-lightening agents have been used globally to enhance skin tone and obtain a magnificent outward appearance. The pigment known as melanin, produced by melanocytes, imparts skin color. The Cosmetic Europe survey testifies that most people believe that cosmetics enhance one's quality of life. The most in-demand in the cosmetics industry are skin-whitening agents. Heavy metals and dangerous substances like lead and mercury are present in these skin-brightening cosmetics, which have a long-term effect on important organs and begin asymptomatic. Despite these negative consequences, there is a sizable market for these products due to the desire for fairer skin tones. Cosmetovigilance studies determine the of heavy metals in these preparations, which need to be monitored regularly. This article discusses the toxicity of heavy metals such as nickel, mercury, arsenic, lead, cobalt, and others found in skin-lightening formulas. The acceptable limit for these toxic agents is recognized by several healthcare organizations worldwide.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Novel Therapeutic Opportunities for Dilated Cardiomyopathy: A Bioinformatics Approach to Drug Repositioning and Herbal Medicine Prediction.","authors":"Jiao Wang, Tianwei Meng, Na Si, Haihong Li, Yan Yan, Xinghua Li","doi":"10.2174/0113892010335576241202061139","DOIUrl":"https://doi.org/10.2174/0113892010335576241202061139","url":null,"abstract":"<p><strong>Background: </strong>Dilated Cardiomyopathy (DCM) is a debilitating cardiovascular disorder that challenges current therapeutic strategies. The exploration of novel drug repositioning opportunities through gene expression analysis offers a promising avenue for discovering effective treatments.</p><p><strong>Objective: </strong>This study aims to identify potential drug repositioning opportunities and lead compounds for DCM treatment by optimizing gene expression characteristics using published data.</p><p><strong>Methods: </strong>Our approach involved analyzing DCM expression profiles from the Gene Expression Omnibus database and identifying differentially expressed genes with GEO2R. A protein interaction network was constructed using the STRING database and visualized with Cytoscape. Enrichment analyses were conducted on these genes through the Omicshare platform, followed by the identification of candidate compounds via the Connectivity Map (CMAP) and validation through molecular docking. The Coremine Medical database was utilized to predict potential herbal medicines.</p><p><strong>Results: </strong>We identified 29 differentially expressed genes, highlighting MYH6, NPPA, and NPPB as central to DCM pathology. Enrichment analyses indicated significant impacts on biological processes, such as organ morphogenesis and inflammatory responses. The AGE-RAGE signaling pathway was notably affected. From over 6,100 compounds analyzed, tenoxicam emerged as a promising candidate, with Radix Salviae Miltiorrhizae (Danshen) being suggested as a potential herbal treatment.</p><p><strong>Conclusion: </strong>This study underscores the utility of bioinformatics in uncovering new therapeutic candidates for DCM, offering a foundational step towards novel drug development.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COL1A1, COL1A2, CHN1, and FN1 Promote Tumorogenesis and Act as Markers of Diagnosis and Survival in Gastric Cancer Patients.","authors":"Yan Yichao, Li Yongbai, Liang Hailiang, Chen Dongbo, Li Bo, Abduh Murshed","doi":"10.2174/0113892010332329241119104430","DOIUrl":"https://doi.org/10.2174/0113892010332329241119104430","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to comprehensively investigate the molecular landscape of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.</p><p><strong>Methodology: </strong>GSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB, cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR, and cell proliferation assay were employed in this study.</p><p><strong>Results: </strong>Analysis of the GSE79973 dataset identified 300 differentially expressed genes (DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using protein-protein interaction network analysis. Subsequent validation across The Cancer Genome Atlas (TCGA) datasets confirmed their up-regulation in GC tissues compared to normal controls. Promoter methylation analysis revealed decreased methylation levels of these hubs in GC tissues, suggesting their potential role in tumorigenesis. Mutational analysis using cBioPortal showcased frequent mutations in these genes, particularly FN1, further highlighting their significance in GC pathogenesis. Survival analysis indicated their correlation with reduced overall survival rates among GC patients, supported by the development of a robust prognostic model. Prediction of hub-associated miRNAs and gene enrichment analysis provided insights into their regulatory mechanisms and downstream pathways, implicating their involvement in extracellular matrix remodeling and cell migration. Drug sensitivity analysis revealed correlations between hub gene expression and drug response, while RT-qPCR validation confirmed their upregulation in clinical GC samples. Finally, functional assays demonstrated the impact of FN1 knockdown on cellular proliferation, colony formation, and wound healing capacities.</p><p><strong>Conclusion: </strong>Overall, this study elucidates the crucial role of COL1A1, COL1A2, CHN1, and FN1 in GC pathogenesis and underscores their potential as diagnostic markers and therapeutic targets.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact and Significance of Viral Vectors for siRNA Delivery in the Treatment of Alzheimer's Disease.","authors":"Chintan Aundhia, Ghanshyam Parmar, Chitrali Talele, Rahul Trivedi, Mamta Kumari, Jay Chudasama","doi":"10.2174/0113892010334094241112190337","DOIUrl":"https://doi.org/10.2174/0113892010334094241112190337","url":null,"abstract":"<p><p>Alzheimer's disease (AD) remains a major challenge in developing effective treatments due to its complex pathophysiology, including the accumulation of amyloid-beta plaques and tau tangles. Small interfering RNA (siRNA) technology offers promise for targeted gene silencing, but effective delivery to the central nervous system remains a significant obstacle. Viral vectors have emerged as potent delivery vehicles for transporting siRNA to neural tissues. This review explores the utilization of viral vectors for siRNA delivery in AD, focusing on delivery strategies and challenges. We discuss the design and optimization of viral vectors, targeting strategies, and safety considerations. Additionally, we examine recent advancements and prospects for enhancing viral vector-mediated siRNA delivery in AD.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic Fe3O4 Nanozymes Promote Apoptosis in Breast Cancer Cell Lines via Free Radical Scavenging and Inhibition of RelA/p65.","authors":"Deepa Mundekkad, William C Cho","doi":"10.2174/0113892010337908241129055322","DOIUrl":"https://doi.org/10.2174/0113892010337908241129055322","url":null,"abstract":"<p><strong>Introduction: </strong>Iron oxide nanozyme was synthesized from the fruit peel extract of pomegranate, which served as a reducing agent during the green synthesis. The scavenging of reactive oxygen species is often accompanied by immunomodulation following antiproliferative effects due to the crosstalk between the proteins involved in the inter-related signaling pathways.</p><p><strong>Method: </strong>In the current study, the green synthesized nanozyme was studied for its ability to induce apoptosis in breast cancer cell lines. The free radical scavenging effect of the nanozyme was reflected as an extension of its intrinsic endogenous enzyme-mimicking property.</p><p><strong>Result & discussion: </strong>The cell cycle analysis revealed that the cell death induced by nanozyme mainly affected the G0/G1 phase. The expression of RelA/p65 and the inflammatory mediators affected by the nanozyme established the role of the Fe3O4 nanozyme in immunomodulation along with its antiproliferative activity.</p><p><strong>Conclusion: </strong>This is the first report on the antiproliferative and immunomodulatory activities expressed by the biomimetic iron oxide nanozyme.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Exosome and its Application in Skin Wound Healing: A Systematic Review on In vitro Studies.","authors":"Mohammad Bagher Heydari, Zahra Ghanbari-Movahed, Maryam Heydari, Mohammad Hosein Farzaei","doi":"10.2174/0113892010323495241016085000","DOIUrl":"https://doi.org/10.2174/0113892010323495241016085000","url":null,"abstract":"<p><strong>Background: </strong>Wound healing is a complex procedure frequently delayed in patients with underlying chronic conditions. Despite essential advances in tissue engineering and regenerative medicine, wound healing remains challenging, warranting novel methods for promoting wound healing. It has been demonstrated that exosomes are one of the main secretory products of different cell types, such as Mesenchymal Stem Cells (MSCs), for regulating various biological processes, including wound healing. Henceforth, understanding these exosome effects might assist in improving wound management and highlight a novel therapeutic model for cell-free therapies with reduced side effects for repairing wounds.</p><p><strong>Methods: </strong>This systematic review involved conducting research electronically on scholarly scientific databases, including PubMed, Science Direct, and Scopus. Eligibility checks were performed based on predefined selection criteria. Finally, thirty-nine studies were considered.</p><p><strong>Results: </strong>Exosomes have been indicated to use multitargeted pathways to improve wound healing by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, metastasis, apoptosis, and angiogenesis.</p><p><strong>Conclusion: </strong>The outcome of this review might guide pre-clinical and clinical studies on the role of exosomes in skin wound healing.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro Investigation of Antimicrobial and Antioxidant Properties of Green Silver Nanoparticles Synthesized Using Ephedra gerardiana Plant Extract.","authors":"Ali Abizi-Moqadam, Sobhan Mortazavi-Derazkola, Majid Zare-Bidaki, Freshteh Osmani, Leili Alizadeh","doi":"10.2174/0113892010349133241120075750","DOIUrl":"https://doi.org/10.2174/0113892010349133241120075750","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of antibiotic-resistant bacteria necessitates exploring nanotechnology as a potential solution for microbial elimination.</p><p><strong>Objectives: </strong>This study aimed to investigate the antimicrobial and antioxidant effects of silver nanoparticles synthesized using aqueous extract from the Ephedra gerardiana (E. gerardiana) plant (EG@AgNPs).</p><p><strong>Methods: </strong>Optimal synthesis conditions, including silver nitrate concentration, time, and temperature, were determined. Characterization of EG@AgNPs was conducted, which was followed by antimicrobial assessment against eight bacterial strains and one fungal strain. Additionally, the antioxidant properties of EG@AgNPs were evaluated using the DPPH method.</p><p><strong>Results: </strong>XRD analysis confirmed EG@AgNPs synthesis. DLS analysis revealed a hydrodynamic diameter of 22 nm. FT-IR analysis confirmed the presence of functional groups from the E. gerardiana plant extract in EG@AgNPs. FESEM and TEM images depicted spherical nanoparticles ranging in size from 10 to 20 nm. Antimicrobial investigations using the broth microdilution method demonstrated that E. gerardiana plant extract at 7.5 mg/ml inhibited only Streptococcus mutans and Candida albicans growth, with no antimicrobial effects observed at lower concentrations. However, EG@AgNPs significantly enhanced the antimicrobial properties of the E. gerardiana plant extract. Notably, these nanoparticles exhibited the most significant effect on E. coli and the least on S. salivaris, with MIC value of 125 and 2000 μg/ml, respectively. Furthermore, they inhibited C. albicans growth at a concentration of 62.5 μg/ml. An assessment of the antioxidant properties of EG@AgNPs indicated a significant increase in antioxidant activity.</p><p><strong>Conclusion: </strong>The E. gerardiana plant extract has emerged as a promising option for silver nanoparticle synthesis. These nanoparticles have been found to exhibit potent antimicrobial properties against Gram-positive and Gram-negative bacterial species, as well as C. albicans. Additionally, they have demonstrated antioxidant properties.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strengthening Effect of Thalidomide Combined with an Anti-PD1 Antibody on Enhancing Immunity for Lung Cancer Therapy.","authors":"Qing Liu, Zu-Chian Chiang, Xiangqian Zhao, Dongya Cui, Xinxin Li, Hao Chen, Fangyu Lin, Tao Jiang, Qi Chen, Xiaoyan Lin, Jizhen Lin","doi":"10.2174/0113892010319495241218114812","DOIUrl":"https://doi.org/10.2174/0113892010319495241218114812","url":null,"abstract":"<p><strong>Objective: </strong>Combining immune checkpoint inhibitors and antiangiogenic agents offers a promising strategy to counteract the cooperative promotion of solid tumor growth by immune checkpoints and intratumoral angiogenesis.</p><p><strong>Methods: </strong>We investigated the potential of thalidomide (THD) and anti-PD-1 antibody (PD-1 mAb) in suppressing tumor growth, enhancing immunity, and inhibiting angiogenesis.</p><p><strong>Results: </strong>THD exhibited regulatory effects on PD-1 in CD4+ T cells and PD-L1 in cancer cells, along with tumor growth inhibition in A549 and Lewis lung carcinoma (LLC) cell lines. Combined with PD-1 mAb, THD increased intracellular IL-2 and IFN-γ expression in CD4+ T cells, enhanced granzyme (Gzm-B) expression in peripheral blood mononuclear cells (PBMCs), and reduced TNF-α expression in CD4+ T cells. In C57BL/6 mice, THD plus PD-1 mAb decreased LLC-derived lung tumor weight and volume, boosted CD8+ T cell infiltration in tumors, and reduced CD34+ intratumoral microvessel density.</p><p><strong>Conclusion: </strong>This study highlights THD's role in modifying the tumor microenvironment to enhance PD-1 mAb efficacy, proposing a clinically feasible approach for improving PD-1 mAb treatment outcomes.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Pseudomonas aeruginosa</i> Recombinant L-asparaginase: PEGylation with Low Molecular Weight Polyethylene Glycol, Molecular Dynamics Simulation, <i>In vitro</i> and <i>In vivo</i> Serum half-life and Biochemical Characterization.","authors":"Rawan Alshamy, Nefertiti El-Nikhely, Hisham Nematalla, Mohamed Elkewedi, Eman Abdallah Mahran, Hesham Saeed","doi":"10.2174/0113892010309260240624072408","DOIUrl":"10.2174/0113892010309260240624072408","url":null,"abstract":"<p><strong>Background: </strong>Microbial L-asparaginase (L-ASNase, EC 3.5.1.1) is a pivotal biopharmaceutical drug-protein that catalyzes the hydrolysis of the non-essential amino acid L-asparagine (L-Asn) into L-aspartic acid (L-Asp) and ammonia , resulting in deplenishing the cellular L-Asn pool, which leads to the ultimate death of the L-asparagine synthetase (L-ASNS) deficient cancerous cells.</p><p><strong>Objective: </strong>This study aimed to investigate the impact of conjugating low molecular weight polyethylene glycol to recombinant <i>P. aeruginosa</i> L-ASNase by examining the pharmacokinetic properties, affinity towards the substrate, and enzyme stability prior to and following the reaction.</p><p><strong>Methods: </strong>The recombinant <i>P. aeruginosa</i> L-ASNase was affinity purified and then PEGylated by attaching polyethylene glycol (MW= 330 Da) site-specifically to the protein's N-terminus end. After which, the PEGylated L-ASNase was examined by SDS-PAGE (15%), FTIR, and UV/Vis spectrophotometry and subsequently biochemically characterized.</p><p><strong>Results: </strong>The Km and Vmax values of free <i>P. aeruginosa</i> rL-ASNase were determined to be 0.318 ±1.76 mM and 2915 μmol min^-1 and following the PEGylation, they were found to be 0.396 ±1.736 mM and 3193 μmol min^-1, respectively. Polyethylene glycol (330 Da) has markedly enhanced LASNase thermostability at 37, 45, 50, and 55°C, as opposed to the free enzyme, which retained 19.5% after 1 h of incubation at 37°C. The PEGylated L-ASNase was found to be stable upon incubation with human serum for 28 h, in contrast to the sharp decline in the residual bioactivity of the free rL-ASNase after 4 h incubation. Accordingly, an <i>in vivo</i> study was used for validation, and it demonstrated that PEGylated rL-ASNase exhibited longer bioactivity for 24 h, while the free form's activity vanished entirely from the rats' blood sera after 8 h. Molecular dynamics simulation indicated that PEG (330 Da) has affected the hydrodynamic volume of L-ASNase and increased its structural stability. Docking analysis has explored the position of PEG with respect to binding sites and predicted a similar binding affinity to that of the free enzyme.</p><p><strong>Conclusion: </strong>For the first time, recombinant L-ASNase was modified by covalently attaching PEG (330 Da). The resultant novel proposed PEGylated rL-ASNase with remarkably increased stability and prolonged <i>in vivo</i> half-life duration, could be considered an alternative to mitigate the high molecular weight of PEGylation's drawbacks.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"617-629"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}