Current protein & peptide science最新文献_第8页

How Useful are Antimicrobial Peptide Properties for Predicting Activity, Selectivity, and Potency? 抗菌肽特性对预测活性、选择性和效力有多大作用？

IF 1.9 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037317887240625054710

Brandt Bertrand, Pablo Luis Hernandez-Adame, Carlos Munoz-Garay

{"title":"How Useful are Antimicrobial Peptide Properties for Predicting Activity, Selectivity, and Potency?","authors":"Brandt Bertrand, Pablo Luis Hernandez-Adame, Carlos Munoz-Garay","doi":"10.2174/0113892037317887240625054710","DOIUrl":"10.2174/0113892037317887240625054710","url":null,"abstract":"Antimicrobial peptides (AMPs) are recognized for their potential application as new generation antibiotics, however, up to date, they have not been widely commercialized as expected. Although current bioinformatics tools can predict antimicrobial activity based on only amino acid sequences with astounding accuracy, peptide selectivity and potency are not foreseeable. This, in turn, creates a bottleneck not only in the discovery and isolation of promising candidates but, most importantly, in the design and development of novel synthetic peptides. In this paper, we discuss the challenges faced when trying to predict peptide selectivity and potency, based on peptide sequence, structure and relevant biophysical properties such as length, net charge and hydrophobicity. Here, pore-forming alpha-helical antimicrobial peptides family isolated from anurans was used as the case study. Our findings revealed no congruent relationship between the predicted peptide properties and reported microbial assay data, such as minimum inhibitory concentrations against microorganisms and hemolysis. In many instances, the peptides with the best physicochemical properties performed poorly against microbial strains. In some cases, the predicted properties were so similar that differences in activity amongst peptides of the same family could not be projected. Our general conclusion is that antimicrobial peptides of interest must be carefully examined since there is no universal strategy for accurately predicting their behavior.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"22-40"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632930","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}

引用次数: 0

Preliminary Analysis of Potentially Overlapping Differentially Expressed Proteins in Both the Spinal Cord and Brain of SOD1 G93A Mice. 对 SOD1 G93A 小鼠脊髓和大脑中潜在重叠差异表达蛋白的初步分析

IF 1.9 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037293525240621120033

Shi-Shi Jiang, Hong-Bing Nie, Shan Hua, Meng Xie, Ren-Shi Xu

{"title":"Preliminary Analysis of Potentially Overlapping Differentially Expressed Proteins in Both the Spinal Cord and Brain of SOD1 G93A Mice.","authors":"Shi-Shi Jiang, Hong-Bing Nie, Shan Hua, Meng Xie, Ren-Shi Xu","doi":"10.2174/0113892037293525240621120033","DOIUrl":"10.2174/0113892037293525240621120033","url":null,"abstract":"Objective: Proteomic elucidation is an essential step in improving our understanding of the biological properties of proteins in amyotrophic lateral sclerosis (ALS).Methods: Preliminary proteomic analysis was performed on the spinal cord and brain of SOD1 G93A (TG) and wild-type (WT) mice using isobaric tags for relative and absolute quantitation.Results: Partial up- and downregulated proteins showing significant differences between TG and WT mice were identified, of which 105 proteins overlapped with differentially expressed proteins in both the spinal cord and brain of progression mice. Bioinformatic analyses using Gene Ontology, a cluster of orthologous groups, and Kyoto Encyclopedia of Genes and Genomes pathway revealed that the significantly up- and downregulated proteins represented multiple biological functions closely related to ALS, with 105 overlapping differentially expressed proteins in the spinal cord and brain at the progression stage of TG mice closely related to 122 pathways. Differentially expressed proteins involved in a set of molecular functions play essential roles in maintaining neural cell survival.Conclusion: This study provides additional proteomic profiles of TG mice, including potential overlapping proteins in both the spinal cord and brain that participate in pathogenesis, as well as novel insights into the up- and downregulation of proteins involved in the pathogenesis of ALS.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"57-75"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562904","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}

引用次数: 0

Unraveling APOE4's Role in Alzheimer's Disease: Pathologies and Therapeutic Strategies. 揭示APOE4在阿尔茨海默病中的作用：病理和治疗策略。

IF 1.9 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037326839241014054430

Siddhant Tripathi, Yashika Sharma, Dileep Kumar

{"title":"Unraveling APOE4's Role in Alzheimer's Disease: Pathologies and Therapeutic Strategies.","authors":"Siddhant Tripathi, Yashika Sharma, Dileep Kumar","doi":"10.2174/0113892037326839241014054430","DOIUrl":"10.2174/0113892037326839241014054430","url":null,"abstract":"Alzheimer's disease (AD), the most common kind of dementia worldwide, is characterized by elevated levels of the amyloid-β (Aβ) peptide and hyperphosphorylated tau protein in the neurons. The complexity of AD makes the development of treatments infamously challenging. Apolipoprotein E (APOE) genes's ε4 allele is one of the main genetic risk factors for AD. While the APOE gene's ε4 allele considerably increases the chance of developing AD, the ε2 allele is protective compared to the prevalent ε3 variant. It is fiercely discussed how APOE affects the development and course of disease since it has a variety of activities that influence both neuronal and non-neuronal cells. ApoE4 contributes to the formation of tau tangles, deposition of Aβ, neuroinflammation, and other processes. Four decades of research have provided a significant understanding of the structure of APOE and how this may affect the neuropathology and pathogenesis of AD. APOE is a crucial lipid transporter essential for the growth of the central nervous system (CNS), upkeep, and repair. The mechanisms by which APOE contributes to the pathophysiology of AD are still up for discussion, though. Evidence suggests that APOE affects the brain's clearance and deposition of Aβ. Additionally, APOE has Aβ-independent pathways in AD, which has led to the identification of new functions for APOE, including mitochondrial dysfunction. This study summarizes important studies that describe how APOE4 affects well-known AD pathologies, including tau pathology, Aβ, neuroinflammation, and dysfunction of neural networks. This study also envisions some of the therapeutic approaches being used to target APOE4 in the hopes of preventing or treating AD.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"259-281"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892118","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}

引用次数: 0

Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences. 铁蛋白阻碍非肿瘤性疾病中的铁蛋白沉积：调节机制和潜在后果。

IF 1.9 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037315874240826112422

Zhongcheng Xie, Qin Hou, Yinling He, Yushu Xie, Qinger Mo, Ziyi Wang, Ziye Zhao, Xi Chen, Tianhong Peng, Liang Li, Wei Xie

引用次数: 0

Transforming Medicine: Advances in Gene Therapy, Immunotherapy, and Targeted Cures. 改变医学：基因治疗、免疫治疗和靶向治疗的进展。

IF 1.9 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037336137250102104842

Komal Gupta, Vikram Sharma, Tohfa Siddiqui

{"title":"Transforming Medicine: Advances in Gene Therapy, Immunotherapy, and Targeted Cures.","authors":"Komal Gupta, Vikram Sharma, Tohfa Siddiqui","doi":"10.2174/0113892037336137250102104842","DOIUrl":"10.2174/0113892037336137250102104842","url":null,"abstract":"In recent years, novel therapeutic approaches have revolutionized the landscape of medicine, offering promising avenues for the cure of various diseases. The novel approaches explore advancements in gene therapy in pharmaceuticals, immunotherapy, RNA-based therapeutics, cell-based therapies, and targeted tumor therapies. Gene therapy has emerged as a groundbreaking approach, leveraging genetic material to cure or prevent diseases by targeting defective genes. In pharmaceuticals, gene therapy holds immense potential for addressing genetic disorders, offering a personalized approach to medicine. Immunotherapy, on the other hand, harnesses the body's immune system to combat diseases, including tumors, by enhancing immune responses or directly targeting malignant cells. RNA-based therapeutics have gained prominence due to their ability to modulate gene expression, offering targeted and precise interventions for a wide range of diseases. Cell-based therapies involve the transplantation or manipulation of cells to restore or enhance their function, offering innovative solutions for diseases such as neurodegenerative disorders and cardiovascular diseases. Furthermore, targeted tumor therapies have revolutionized tumor cure by specifically targeting molecular alterations driving tumor growth and minimizing damage to healthy cells. Overall, these novel therapeutic approaches represent a paradigm shift in medicine, offering tailored and precise interventions with the potential to significantly improve patient outcomes and quality of life.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"436-450"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058334","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}

引用次数: 0

Circulating SFRP2 in Iranian Polycystic Ovarian Syndrome Patients with Infertility and Recurrent Pregnancy Loss and its Correlation with Insulin Resistance and Inflammation. 伊朗多囊卵巢综合征不孕和复发性流产患者循环SFRP2及其与胰岛素抵抗和炎症的相关性

IF 2 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037339007250120100322

Ali Abdul Kareem Jawad, Fariba Nabatchian, Nariman Moradi, Hamid Choobineh, Reza Fadaei, Reza Afrisham

{"title":"Circulating SFRP2 in Iranian Polycystic Ovarian Syndrome Patients with Infertility and Recurrent Pregnancy Loss and its Correlation with Insulin Resistance and Inflammation.","authors":"Ali Abdul Kareem Jawad, Fariba Nabatchian, Nariman Moradi, Hamid Choobineh, Reza Fadaei, Reza Afrisham","doi":"10.2174/0113892037339007250120100322","DOIUrl":"10.2174/0113892037339007250120100322","url":null,"abstract":"Introduction: Secreted Frizzled-Related Protein 2 (SFRP2) is considered to be the most potent modulator of the Wnt signaling. This pathway is involved in the pathogenesis of Polycystic Ovary Syndrome (PCOS). This research aimed to compare the levels of SFRP2 in PCOS [infertile and Recurrent Pregnancy Loss (RPL) patients] with the control group and determine the correlation of SFRP2 with inflammation and insulin resistance.Methods: This case-control study was conducted on 108 POCS patients (53 infertile patients and 55 women with RPL) and 54 healthy controls. The levels of biochemical factors along with SFRP2, adiponectin, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), free testosterone, and insulin, high-sensitivity C-Reactive Protein (hs-CRP) were measured following the manufacturer's instructions.Results: Both infertile and RPL groups presented notably higher levels of SFRP2 (49.32 ± 17.72 ng/ml and 55.89 ± 17.36 ng/ml, respectively) compared to the control group (30.21 ± 10.12 ng/ml, P<0.001 for both groups). In PCOS patients, a positive correlation was observed between SFRP2 and body mass index (BMI) (r = 0.42, P < 0.001), insulin (r = 0.19, P = 0.04), fasting blood glucose (FBG) (r = 0.24, P = 0.01), Homeostatic Model Assessment for Insulin Resistance (HOMA- IR) (r = 0.21, P = 0.03), triglyceride (r = 0.25, P = 0.009), and hs-CRP (r = 0.21, P = 0.02). Furthermore, SFRP2 increased the risk of RPL (OR (95% CI) = 1.15 (1.10 -1.20), P < 0.001) and infertility (OR (95% CI) = 1.12 (1.07 -1.17), P < 0.001) in comparison with the controls.Conclusion: Our findings suggested that SFRP2 may have a potential involvement in the development of PCOS and might be a promising target for diagnosis, but additional research is required to confirm this.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"585-592"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406207","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}

引用次数: 0

Purification, Characterization, and Antimicrobial Activity Against Candida parapsilosis and Staphylococcus aureus of a Highly Stable Type-1 Cystatin from Terminalia catappa L. Seeds. 高稳定型半胱抑素的纯化、鉴定及对假丝酵母菌和金黄色葡萄球菌的抑菌活性研究

IF 1.9 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037339021241017084509

Amanda M A Moura, Jose Tadeu A Oliveira, Daniele O B Sousa, Lucas P Dias, Nadine M S Araujo, Raquel de O Rocha, Tawanny K B Aguiar, Joao M M Neto, Viviane O Silva, Ricardo M Feitosa, Queilane L S G Chaves, Marcio V Ramos, Cleverson D T Freitas

{"title":"Purification, Characterization, and Antimicrobial Activity Against Candida parapsilosis and Staphylococcus aureus of a Highly Stable Type-1 Cystatin from Terminalia catappa L. Seeds.","authors":"Amanda M A Moura, Jose Tadeu A Oliveira, Daniele O B Sousa, Lucas P Dias, Nadine M S Araujo, Raquel de O Rocha, Tawanny K B Aguiar, Joao M M Neto, Viviane O Silva, Ricardo M Feitosa, Queilane L S G Chaves, Marcio V Ramos, Cleverson D T Freitas","doi":"10.2174/0113892037339021241017084509","DOIUrl":"10.2174/0113892037339021241017084509","url":null,"abstract":"Introduction: Clinic infections caused by various microorganisms are a public health concern. The rise of new strains resistant to traditional antibiotics has exacerbated the problem. Thus, the search for new antimicrobial molecules remains highly relevant.Methods: The current study purified, characterized, and assessed the antimicrobial activity of a papain inhibitor from Terminalia catappa L. seeds.Results: The inhibitor was purified by heating the crude extract at 80°C for 30 min, followed by ion exchange chromatography on a DEAE cellulose column. The purification index was 9-fold, yielding 2.3%. SDS-PAGE and size exclusion chromatography revealed that the protease inhibitor (TcPI) is a 15.9 kDa monomeric protein. The inhibition kinetics showed that TcPI is a competitive inhibitor specific to papain (Ki = 1.02 x 10-4 M). TcPI remained active even after heating at 100oC for 120 min and at pH conditions varying from 2.0 to 10.0. Even after 60 min, TcPI was resistant to papain proteolysis. TcPI exhibited antimicrobial activity against Candida parapsilosis and Staphylococcus aureus. Conclusion: Here, we show that TcPI is a highly stable type-1 cystatin with the potential to combat infections caused by C. parapsilosis and S. aureus. Additional investigations into TcPI's structural aspects and mechanism of action, as well as safety assessments, are essential prerequisites for its potential application as a novel therapeutic intervention.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"308-319"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892820","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}

引用次数: 0

Synergistic Effects of Hydrogen Peroxide Preconditioning and Valproic Acid on Hepatic Differentiation of Mesenchymal Stem Cells. 过氧化氢预处理和丙戊酸对间充质干细胞肝分化的协同作用。

IF 2 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037343658241111051831

Saman Rashid, Asmat Salim, Nadia Naeem, Kanwal Haneef

{"title":"Synergistic Effects of Hydrogen Peroxide Preconditioning and Valproic Acid on Hepatic Differentiation of Mesenchymal Stem Cells.","authors":"Saman Rashid, Asmat Salim, Nadia Naeem, Kanwal Haneef","doi":"10.2174/0113892037343658241111051831","DOIUrl":"10.2174/0113892037343658241111051831","url":null,"abstract":"Introduction: Ex vivo preconditioning increases the therapeutic potential of mesenchymal stem cells (MSCs) in terms of antioxidant activity, growth factor production, homing, differentiation, and immunomodulation. Therefore, it is considered an effective strategy to be used before transplantation and therapeutic application of MSCs. Histone deacetylase inhibitor (HDACi), valproic acid (VPA), has been reported to induce hepatic differentiation in MSCs. Although individual studies have shown that preconditioning and epigenetic modification enhance the survival and differentiation of MSCs, the combined effects of these therapies have not been fully explored. This study aims to investigate the combined effect of hydrogen peroxide (H2O2) preconditioning and HDACi (valproic acid) on the differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into hepatic-like cells.Methods: MSCs were first preconditioned with H2O2 and then cultured with VPA. The migration and proliferation potential of the treated cells were evaluated using wound healing and colonyforming unit assays. Furthermore, the expression of hepatic genes (FOXA2, CK8, CK18, TAT) and proteins (AFP, ALB, TAT) was evaluated in all treated groups.Results: The combined therapy group exhibited enhanced cell migration and proliferation, as evidenced by wound healing and colony-forming unit assays. Additionally, the combined treatment group showed higher expression of FOXA2, CK8, and CK18 hepatic genes and TAT protein, suggesting an improved differentiation of stem cells into hepatocytes.Conclusion: In conclusion, the combination of H2O2 and VPA emerges as an important factor in promoting hepatocyte differentiation. However, further studies are required to optimize this protocol for future therapeutics.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"546-555"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946119","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}

引用次数: 0

In-vitro, In-silico Investigations Reveals Potential Cytotoxic Activity of Fermentation Metabolites from Actinomycetes Isolated from Lonar Soda Lake Against HeLa Cancer Cell Lines. 体外，计算机研究揭示了从Lonar Soda湖分离的放线菌发酵代谢产物对HeLa癌细胞的潜在细胞毒活性。

IF 1.9 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037334392241216074545

Pradip Bawane, Santosh Yele

{"title":"In-vitro, In-silico Investigations Reveals Potential Cytotoxic Activity of Fermentation Metabolites from Actinomycetes Isolated from Lonar Soda Lake Against HeLa Cancer Cell Lines.","authors":"Pradip Bawane, Santosh Yele","doi":"10.2174/0113892037334392241216074545","DOIUrl":"10.2174/0113892037334392241216074545","url":null,"abstract":"Background: Actinomycetes, Gram-positive bacteria, are recognized for producing bioactive metabolites. Lonar Soda Lake, an alkaline ecosystem, hosts diverse actinomycetes with possible anticancer activities.Aim: To assess the cytotoxic potential of fermentation metabolites from actinomycetes isolated from Lonar Soda Lake against HeLa cancer cells employing in-vitro and in-silico methods.Objectives: Evaluate the cytotoxicity of fermentation metabolites from Lonar Lake actinomycetes on HeLa cells. Execute molecular docking to forecast metabolite connections with cancer-related proteins.Materials and methods: The actinomycetes were isolated from the sediment sample of Lonar Lake using a selective medium and recognized by gene sequencing. Cytotoxicity on HeLa cells was assessed using the MTT assay, in consort with oxidative stress and apoptotic markers (GSH, MDA, TNF-α, and caspase 3). Molecular docking and molecular dynamics studies evaluated metabolite binding to cancer-related proteins (Bcl-2, TNF-α, caspase 3).Results: Fermentation metabolites of three Lonar Lake Sediment isolates (LLSD), LLSD-5, LLSD- 7, and LLSD-9 showing promising cytotoxic activity against HeLa cell lines by MTT assay, also significantly modulate the oxidative stress parameters (GSH, MDA), and cell apoptotic marker (TNF-α, caspase 3). IC50 values were 34.17 μM (LLSD-5), 53.85 μM (LLSD-7), and 69.54 μM (LLSD-9). Furthermore, molecular docking displayed robust binding affinities to cancer-related proteins, uncovering the possible mechanism of action.Conclusion: The fermentation metabolites actinomycete isolates from Lonar Lake exhibit significant cytotoxic activity against HeLa cancer cell lines. Both in-vitro and in-silico analyses support the potential of these metabolites as anticancer agents.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"378-391"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946114","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}

引用次数: 0

Discovery of Sulfanilamide-diazo Derivatives Incorporating Benzoic Acid Moieties as Novel Inhibitors of Human Carbonic Anhydrase II Activity. 含有苯甲酸基团的磺胺类重氮衍生物作为人类碳酸酐酶II活性的新抑制剂的发现。

IF 1.9 4区生物学

Current protein & peptide science Pub Date : 2025-01-01 DOI: 10.2174/0113892037332139241008054602

Farshid Belani, Maryam Mehrabi, Hadi Adibi, Masomeh Mehrabi, Reza Khodarahmi

{"title":"Discovery of Sulfanilamide-diazo Derivatives Incorporating Benzoic Acid Moieties as Novel Inhibitors of Human Carbonic Anhydrase II Activity.","authors":"Farshid Belani, Maryam Mehrabi, Hadi Adibi, Masomeh Mehrabi, Reza Khodarahmi","doi":"10.2174/0113892037332139241008054602","DOIUrl":"10.2174/0113892037332139241008054602","url":null,"abstract":"Background: Sulfonamides are widely used carbonic anhydrase inhibitors (CAIs) in clinical settings, however, their nonspecific inhibition of multiple carbonic anhydrase isoforms can lead to reduced efficacy and side effects. This study aimed to develop sulfanilamide-diazo derivatives incorporating benzoic acid moieties as novel inhibitors of hCA II activity to reduce side effects and enhance selectivity for different CA isozymes.Methods: We investigated the interaction between these derivatives and the hCA II isozyme via various spectroscopic and docking methods.Results: The kinetic data demonstrates that compound 1 (C1) and compound 2 (C2) share a similar inhibitory strength against hCA II, effectively inhibiting its esterase activity through a noncompetitive mechanism with Ki values at low micromolar levels. Fluorescence measurements indicated that the synthesized compounds suppressed the inherent fluorescence of hCA II via a static quenching process, with each compound showing a singular binding site within the enzyme. Thermodynamic evidences highlight the significance of van der Waals interactions and hydrogen bonding in the binding process. The results of molecular docking indicated that both C1 and C2 effectively obstruct the entrance to hCA II's active site, with no significant differences in their binding conformations.Conclusion: While C1 and C2 exhibit CA inhibitory potency lower than that of sulfonamide compounds, this study offers valuable insights that could pave the way for the development of a promising scaffold for designing new carbonic anhydrase inhibitors.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"226-240"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794545","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}

引用次数: 0