Current protein & peptide science最新文献

{"title":"Comparative Proteomic Analysis of Cell Wall Proteins of Aminoglycosides Resistant and Sensitive Mycobacterium tuberculosis Clinical Isolates.","authors":"Devesh Sharma, Sakshi Gautam, Nalini Srivastava, Abdul Mabood Khan, Deepa Bisht","doi":"10.2174/0113892037334796240927055243","DOIUrl":"https://doi.org/10.2174/0113892037334796240927055243","url":null,"abstract":"<p><strong>Introduction: </strong>The rising prevalence of Mycobacterium tuberculosis (M.tb) strains resistant to aminoglycosides (amikacin and kanamycin) challenges effective TB control and treatment. Understanding the mechanisms behind this resistance is crucial since aminoglycosides are a mainstay of TB therapy.</p><p><strong>Aim: </strong>The study aimed to analyze the cell wall proteins overexpressed in aminoglycoside-resistant isolates of Mycobacterium tuberculosis using proteomics approaches.</p><p><strong>Methods: </strong>We used two-dimensional electrophoresis and mass spectrometry to compare the cell wall proteomes of aminoglycosides-resistant and susceptible clinical isolates. The overexpressed protein spots were excised and identified using liquid chromatography-mass spectrometry (LC/MS). The identified proteins were subsequently analyzed for molecular docking, pupylation site identification, and STRING analysis.</p><p><strong>Results: </strong>We found a total of nine significantly upregulated proteins in aminoglycosides-resistant isolates. Three of these proteins were the same (isoform), resulting in the identification of seven unique proteins. Specifically, Rv3841 and Rv1308 belonged to intermediary metabolism and respiration; Rv2115c to the cell wall and cell processes; Rv2501c, Rv2247 and Rv0295c to lipid metabolism; and Rv2416c to virulence, detoxification/adaptation. Notably, variations in these proteins support cell wall integrity, aiding mycobacteria's establishment and proliferation. Molecular docking study revealed that both drugs bind strongly to the proteins' active site regions. Additionally, the GPS-PUP algorithm successfully identified possible pupylation sites within these proteins, except Rv0295c. Based on interactome analysis using the STRING 12.0 database, we have identified potential interactive partners suggesting their role in aminoglycosides resistance.</p><p><strong>Conclusion: </strong>Overexpressed proteins not only act to counteract or regulate drug effects but also have a role in protein dynamics that allow for resistance. Some of these identified proteins may serve as innovative drug targets and biomarkers for the early detection of drug-specific resistance in M.tb. Further research is needed to elucidate the mechanisms by which these potential protein targets contribute to resistance in AK and KM M.tb isolates.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603583","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":"Myotoxicity of Crotoxin on C2C12 Myoblasts and its Inhibition by Crotalus Neutralizing Factor versus Enhanced Resistance in Myotubes: Exploring Toxicity and Membrane Potential.","authors":"Maria Naiara Macedo Tavares, Micaela de Melo Cordeiro Eulálio, Hallison Mota Santana, Charles Nunes Boeno, Valdison Pereira Dos Reis, Cristina Matiele Alves Rego, Alex Augusto Ferreira E Ferreira, Mauro Valentino Paloschi, Andreimar M Soares, Consuelo Latorre Fortes-Dias, Sulamita Silva Setúbal, Juliana Pavan Zuliani","doi":"10.2174/0113892037317894240926081324","DOIUrl":"10.2174/0113892037317894240926081324","url":null,"abstract":"<p><strong>Background: </strong>Crotalus Neutralizing Factor (CNF) is a γ-type Phospholipase A2 (PLA2) inhibitor present in the blood of Crotalus durissus terrificus snake. Particularly, CNF inhibits the toxic action of Crotoxin (CTX), which is a major neurotoxin found in C. d. terrificus venom. CTX induces also myotoxic action and demonstrates high selectivity for skeletal muscle fibers. Consequently, CTX can diffuse beyond the site of infection, which can potentially evoke rhabdomyolysis. The present study has evaluated the effects of CTX on myoblasts and myotubes of muscle cells C2C12 in vitro and the effect of CNF on CTX-induced damage.</p><p><strong>Methods: </strong>Cytotoxicity assays were performed by measuring the mitochondrial enzyme dehydrogenase levels. Furthermore, creatine kinase and lactate dehydrogenase levels were used as indicators of muscle damage.</p><p><strong>Results: </strong>Crotoxin has been found to have cytotoxic effects on C2C12 myoblast cells, while CNF has not shown toxic effects on these cells. Furthermore, the findings have shown CNF (50 μg/mL) to abolish CTX toxicity in myoblasts. The myotubes, differentiated cells, showed no change in mitochondrial respiration when exposed to CNF or CTX, showing greater resistance to the toxic actions of crotoxin.</p><p><strong>Conclusion: </strong>The data have confirmed the potential of CNF as an anti-myotoxic agent to prevent CTX-damaged myoblasts and increase resistance to the toxic effects of crotoxin on differentiated cells.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590454","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":"A Study on the Rationality of Baicalein in the Treatment of Osteoporosis: A Narrative Review.","authors":"Qi Li, Xingyan Ma, Xiaodong Xu, Chengming Zhang, Weiguo Wang","doi":"10.2174/0113892037325783240912072039","DOIUrl":"https://doi.org/10.2174/0113892037325783240912072039","url":null,"abstract":"<p><p>Baicalein (BN) is an active ingredient naturally present in Chinese herbs, such as Scutellaria baicalein, Coptis chinensis, and Dendrobium officinale. It has a variety of pharmacological activities, including antioxidant, anti-inflammatory and antibacterial effects. Therefore, Baicalein (BN) is widely used in the field of medicine and is considered a potential natural medicine. Osteoporosis (OP) is a bone metabolic disease characterized by decreased bone mineral density and bone structure destruction, which is mainly caused by decreased bone formation and increased bone resorption. With the continuous development of molecular biology, the signaling pathways and gene targets of bone metabolism are also expanding. Recent studies have shown that baicalein may affect the function of osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells through MAPK/ERK and MAPKs/NF-κB signaling pathways, so as to have a therapeutic effect on OP. However, the specific mechanism of baicalein in the treatment of OP is still unclear. This article reviews the literature, analyzes and summarizes the mechanism of action of baicalein, and discusses its potential in the prevention and treatment of OP, so as to provide a basis for the clinical application of baicalein.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544256","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":"Utilizing AfDesign for Developing a Small Molecule Inhibitor of PICK 1-PDZ.","authors":"Emily Hendrix, Xinyu Xia, Amy O Stevens, Yi He","doi":"10.2174/0113892037316932240806102854","DOIUrl":"https://doi.org/10.2174/0113892037316932240806102854","url":null,"abstract":"<p><strong>Introduction: </strong>The PICK1 PDZ domain has been identified as a potential drug target for neurological disorders. After many years of effort, a few inhibitors, such as TAT-C5 and mPD5, have been discovered experimentally to bind to the PDZ domain with a relatively high binding affinity. With the rapid growth of computational research, there is an urgent need for more efficient computational methods to design viable ligands that target proteins.</p><p><strong>Method: </strong>Recently, a newly developed program called AfDesign (part of ColabDesign) at https:// github.com/sokrypton/ColabDesign), an open-source software built on AlphaFold, has been suggested to be capable of generating ligands that bind to targeted proteins, thus potentially facilitating the ligand development process. To evaluate the performance of this program, we explored its ability to target the PICK1 PDZ domain, given our current understanding of it. We found that the designated length of the ligand and the number of recycles play vital roles in generating ligands with optimal properties.</p><p><strong>Results: </strong>Utilizing AfDesign with a sequence length of 5 for the ligand produced the highest comparable ligands to that of prior identified ligands. Moreover, these designed ligands displayed significantly lower binding energy compared to manually created sequences.</p><p><strong>Conclusion: </strong>This work demonstrated that AfDesign can potentially be a powerful tool to facilitate the exploration of the ligand space for the purpose of targeting PDZ domains.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016659","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":"Liquid-Liquid Phase Separation Associated with Intrinsically Disordered Proteins: Experimental and Computational Tools.","authors":"Orkid Coskuner-Weber, Vladimir N Uversky","doi":"10.2174/0113892037314062240618193044","DOIUrl":"https://doi.org/10.2174/0113892037314062240618193044","url":null,"abstract":"<p><p>The phenomenon of Liquid-Liquid Phase Separation (LLPS) serves as a vital mechanism for the spatial organization of biomolecules, significantly influencing the elementary processes within the cellular milieu. Intrinsically disordered proteins, or proteins endowed with intrinsically disordered regions, are pivotal in driving this biophysical process, thereby dictating the formation of non-membranous cellular compartments. Compelling evidence has linked aberrations in LLPS to the pathogenesis of various neurodegenerative diseases, underscored by the disordered proteins' proclivity to form pathological aggregates. This study meticulously evaluates the arsenal of contemporary experimental and computational methodologies dedicated to the examination of intrinsically disordered proteins within the context of LLPS. Through a discerning discourse on the capabilities and constraints of these investigative techniques, we unravel the intricate contributions of these ubiquitous proteins to LLPS and neurodegeneration. Moreover, we project a future trajectory for the field, contemplating on innovative research tools and their potential to elucidate the underlying mechanisms of LLPS, with the ultimate goal of fostering new therapeutic avenues for combating neurodegenerative disorders.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advancement in Novel Wound Healing Therapies by Using Antimicrobial Peptides Derived from Humans and Amphibians","authors":"Trilochan Satapathy, Yugal Kishore, Ravindra Kumar Pandey, Shiv Shankar Shukla, Shiv Kumar Bhardwaj, Beena Gidwani","doi":"10.2174/0113892037288051240319052435","DOIUrl":"https://doi.org/10.2174/0113892037288051240319052435","url":null,"abstract":": The skin is the biggest organ in the human body. It is the first line of protection against invading pathogens and the starting point for the immune system. The focus of this review is on the use of amphibian-derived peptides and antimicrobial peptides (AMPs) in the treatment of wound healing. When skin is injured, a chain reaction begins that includes inflammation, the formation of new tissue, and remodelling of existing tissue to aid in the healing process. Collaborating with non-immune cells, resident and recruited immune cells in the skin remove foreign invaders and debris, then direct the repair and regeneration of injured host tissues. Restoration of normal structure and function requires the healing of damaged tissues. However, a major issue that slows wound healing is infection. AMPs are just one type of host-defense chemicals that have developed in multicellular animals to regulate the immune response and limit microbial proliferation in response to various types of biological or physical stress. Therefore, peptides isolated from amphibians represent novel therapeutic tools and approaches for regenerating damaged skin. Peptides that speed up the healing process could be used as therapeutic lead molecules in future research into novel drugs. AMPs and amphibian-derived peptides may be endogenous mediators of wound healing and treat non-life-threatening skin and epithelial lesions. Hence, this article describes different peptides used in wound healing, theirmethods of preparation, and their routes of administration.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":"15 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140887743","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":"Influences of Ipomoea batatas Anti-Cancer Peptide on Tomato Defense Genes","authors":"Hsin-Hung Lin, Kuan-Hung Lin, Yung-Lin Tsai, Rong-Jane Chen, Yen-Chang Lin, Yu-Chi Chen","doi":"10.2174/0113892037299818240408053000","DOIUrl":"https://doi.org/10.2174/0113892037299818240408053000","url":null,"abstract":"Aims: This study investigates the impact of IbACP (Ipomoea batatas anti-cancer peptide) on defense-related gene expression in tomato leaves, focusing on its role in plant defense mechanisms. Background: IbACP was isolated from sweet potato leaves, and it was identified as a peptide capable of inducing an alkalinization response in tomato suspension culture media. Additionally, IbACP was found to regulate the proliferation of human pancreatic adenocarcinoma cells. Objective: Elucidate IbACP's molecular influence on defense-related gene expression in tomato leaves using next-generation sequencing analysis. method: To assess the impact of IbACP on defense-related gene expression, transcriptome data were analyzed, encompassing various functional categories such as photosynthesis, metabolic processes, and plant defense. Semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis was employed to verify transcription levels of defense-related genes in tomato leaves treated with IbACP. Method: To assess the impact of IbACP on defense-related gene expression, transcriptome data were analyzed, encompassing various functional categories such as photosynthesis, metabolic processes, and plant defense. Semi-quantitative reverse-transcription polymerase chain reaction analysis was employed to verify transcription levels of defense-related genes in tomato leaves treated with IbACP for durations ranging from 0 h (control) to 24 h. Results: IbACP induced jasmonic acid-related genes (LoxD and AOS) at 2 h, with a significant up-regulation of salicylic acid-dependent gene NPR1 at 24 h. This suggested a temporal antagonistic effect between jasmonic acid and salicylic acid during the early hours of IbACP treatment. Downstream ethylene-responsive regulator genes (ACO1, ETR4, and ERF1) were consistently down-regulated by IbACP at all times. Additionally, IbACP significantly up-regulated the gene expressions of suberization-associated anionic peroxidases (TMP1 and TAP2) at all time points, indicating enhanced suberization of the plant cell wall to prevent pathogen invasion. Conclusion: IbACP enhances the synthesis of defense hormones and up-regulates downstream defense genes, improving the plant's resistance to biotic stresses.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":"42 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836951","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":"Dominant Circulating Cell-free Mycobacterial Proteins in in-use Machining Fluid and their Antigenicity Potential","authors":"Harish Chandra, Bethany Ahlers, Ying Wai Lam, Jagjit S. Yadav","doi":"10.2174/0113892037291635240405042554","DOIUrl":"https://doi.org/10.2174/0113892037291635240405042554","url":null,"abstract":"Background: Occupational exposure to industrial Metalworking Fluid (MWF) colonized by Mycobacterium immunogenum (MI) has been associated with immune lung disease hypersensitivity pneumonitis (HP) in machinists. This warrants regular fluid monitoring for early detection of mycobacterial proteins, especially those with antigenic potential. Objective: To detect and identify dominant MI proteins and antigens directly from the field-drawn in-use MWF using an integrated immunoproteomic and immunoinformatic approach. Methods: An MI-positive MWF selected by DNA-based screening of several field-drawn MWF samples were cultured to isolate the colonizing strain and profiled for dominant circulating cell- free (ccf) MI proteins, including antigens using an integrated immunoproteomic (1D- and 2Dgel fractionation of seroreactivity proteins combined with shotgun proteomic analysis using LC-MS/ MS) and immunoinformatic strategy. Results: A new MI strain (MJY-27) was identified. The gel fractionated MI protein bands (1Dgel) or spots (2D-gel) seroreactive with anti-MI sera probes (Rabbit and Patient sera) yielded 86 MI proteins, 29 of which showed peptide abundance. T-cell epitope analysis revealed high (90-100%) binding frequency for HLA-I&amp; II alleles for 13 of the 29 proteins. Their antigenicity analysis revealed the presence of 6 to 37 antigenic determinants. Interestingly, one of the identified candidates corresponded to an experimentally validated strong B- and T-cell antigen (AgD) from our laboratory culture-based studies. result: A new MI strain (MJY-27) was identified. The gel fractionated MI protein bands (1D-gel) or spots (2D-gel) seroreactive with anti-MI sera probes (Rabbit and Patient sera) yielded 86 MI proteins, 29 of which showed peptide abundance. T-cell epitope analysis revealed high (90-100%) binding frequency for HLA-I&amp;amp; II alleles for 13 of the 29 proteins. Their antigenicity analysis revealed presence of 6 to 37 antigenic determinants. Interestingly, one of the identified candidates corresponded to an experimentally validated strong B- and T- cell antigen (AgD) from our laboratory culture-based studies. Conclusion: This first report on dominant proteins, including putative antigens of M. immunogenum prevalent in field in-use MWF, is a significant step towards the overall goal of developing fluid monitoring for exposure and disease risk assessment for HP development in machining environments. conclusion: This first report on dominant proteins including putative antigens of M. immunogenum prevalent in field in-use MWF is a significant step towards the overall goal of development of fluid monitoring for exposure and disease risk assessment for HP development in machining environments.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":"27 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837404","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":"Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis","authors":"Feng Cai, Hongbo Xu, Shilong Song, Gengming Wang, Yajun Zhang, Jing Qian, Lu Xu","doi":"10.2174/0113892037287640240322084946","DOIUrl":"https://doi.org/10.2174/0113892037287640240322084946","url":null,"abstract":"Background: Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited. background: Ubiquitin-conjugating enzyme 2T (UBE2T) has been associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. Methods: UBE2T expression in HNSC patient samples and the correlation between its expression and patients’ survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. objective: To study the understanding of its regulatory role in the carcinogenesis of head and neck squamous cell carcinoma (HNSC). Results: The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling and induced ferroptosis in HNSC. method: UBE2T expression in HNSC patient samples and the correlation between its expression and patients’ survival rates were evaluated using TCGA database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T-derived lentivirus. Cell line-derived xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. Conclusion: Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target. result: High expression of UBE2T were consistently observed in HNSC tumor tissues, which correlated with a significantly shortened overall survival time among HNSC patients. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling activation and induced ferroptosis in HNSC.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":"85 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578041","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":"Targeted Delivery of Diphtheria Toxin into VEGFR1/VEGFR2 Overexpressing Cells Induces Anti-angiogenesis Activity","authors":"Fatemeh Kazemi-Lomedasht, Farzad Taghizadeh-Hesary, Zahra Faal, Mahdi Behdani","doi":"10.2174/0113892037292385240222074908","DOIUrl":"https://doi.org/10.2174/0113892037292385240222074908","url":null,"abstract":"Background: Vascular Endothelial Growth Factor Receptors (VEGFR1 and VEGFR2) are tyrosine kinase receptors expressed on endothelial cells and tumor vessels and play an important role in angiogenesis. In this study, three repeats of VEGFR1 and VEGFR2 binding peptide (VGB3) were genetically fused to the truncated diphtheria toxin (TDT), and its in vitro activity was evaluated. Methods: The recombinant construct (TDT-triVGB3) was expressed in bacteria cells and purified with nickel affinity chromatography. The binding capacity and affinity of TDT-triVGB3 were evaluated using the enzyme-linked immunosorbent assay. The inhibitory activity of TDT-triVGB3 on viability, migration, and tube formation of human endothelial cells was evaluated using MTT, migration, and tube formation assays. Results: TDT-triVGB3 selectively detected VEGFR1 and VEGFR2 with high affinity in an enzyme- linked immunosorbent assay and significantly inhibited viability, migration, and tube formation of human endothelial cells. Conclusion: The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":"134 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140197792","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}