International Journal of Peptide Research and Therapeutics最新文献_第4页

Design and Characterization of Anticancer Peptides Derived from Snake Venom Metalloproteinase Library 从蛇毒金属蛋白酶库中提取的抗癌多肽的设计与表征

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-03-27 DOI: 10.1007/s10989-024-10602-0

S. Saranya, M. Bharathi, N. Senthil Kumar, P Chellapandi

{"title":"Design and Characterization of Anticancer Peptides Derived from Snake Venom Metalloproteinase Library","authors":"S. Saranya, M. Bharathi, N. Senthil Kumar, P Chellapandi","doi":"10.1007/s10989-024-10602-0","DOIUrl":"https://doi.org/10.1007/s10989-024-10602-0","url":null,"abstract":"Snake venom metalloproteinases (SVMPs) are enzymatic proteins found in snake venom and are known for their diverse biological activities, including induction of hemorrhage and degradation of fibrinogen. This study aimed to design and characterize anticancer peptides (ACPs) derived from an SVMP library based on their physicochemical properties. A comprehensive analysis predicted 185 ACPs and 177 non-ACPs from 652 SVMPs using a SVM algorithm. Among these, only 23 ACPs demonstrated the ability to penetrate cell membranes, of which 5 were selected as promising candidates. A reliable SVM and confidence scores were obtained for all ACP predictions. The predicted ACPs showed optimal hydrophobicity and favorable structural stability in plasma. The predicted ACPs were characterized by low solubility, high rigidity, and high interaction potential based on their net charge, net hydrogen, and steric hindrance. Among the five ACPs, ACP1 (GDLAAIRKRV) and ACP3 (GDETEIRSRI) had unique amino acid compositions, specifically arginine, lysine, aspartic acid, glutamic acid, and α-helical structures. Molecular docking simulations indicated their interactions with various cancer target proteins, leading to inhibit tumor cell proliferation or migration. In conclusion, ACP01 and ACP03 are potential candidates for the future treatment of breast cancer and leukemia.","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"45 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140311337","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 and in silico Evaluation of the Anti-Biofilm Activity of Histatin 5 against Streptococcus mutans 对组蛋白 5 对抗变异链球菌生物膜活性的体外和硅学评估

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-03-26 DOI: 10.1007/s10989-024-10601-1

Shiva Golshani, Aida Iraji, Zeinab Kadkhoda, Alireza Vatanara

{"title":"In vitro and in silico Evaluation of the Anti-Biofilm Activity of Histatin 5 against Streptococcus mutans","authors":"Shiva Golshani, Aida Iraji, Zeinab Kadkhoda, Alireza Vatanara","doi":"10.1007/s10989-024-10601-1","DOIUrl":"https://doi.org/10.1007/s10989-024-10601-1","url":null,"abstract":"Dental caries is a prevalent and costly disease throughout the world. Streptococcus mutans is widely recognized as one of the key contributing factors in the development of dental caries. Major virulence factors associated with the cariogenicity of S. mutans include adhesion, formation biofilm, acidogenicity and acidurity. Histatin 5, a salivary antimicrobial peptide, exhibited therapeutic effects in the oral cavity. The aim of this study was to evaluate the potential anti-biofilm effects of histatin 5 against S. mutans via in vitro and in silico approaches. Also, the impact of histatin 5 on acidogenicity and acidurity was accessed. The resazurin microdilution method was used to evaluate the anti-biofilm and anti-adhesive activity. Furthermore, molecular docking was carried out to identify the crucial structural features of histatin 5 in binding to glucansucrase enzyme of S. mutans, which is involved in biofilm formation. The findings showed that histatin 5 considerably inhibited the biofilm formation of S. mutans in a dose-dependent manner and could potentially limit the acidogenicity and acidurity of S. mutans. The results of confocal laser scanning microscopy indicated the inhibitory effects of histatin 5 on biofilm formation of S. mutans cells. Moreover, histatin 5 displayed a favorable interaction with glucansucrase, which suggests that it could potentially act as an inhibitor for this enzyme. These findings suggest that histatin 5 could be a promising candidate for the development of a new efficient therapeutic agent for the prevention and treatment of dental caries.","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"39 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140298746","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 Antiviral Activity of Two Host Defense Peptides Against Human alphaherpesvirus 1 两种宿主防御肽对人α疱疹病毒 1 的体外抗病毒活性

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-03-18 DOI: 10.1007/s10989-024-10597-8

Gisele Regina Rodrigues, Rhayfa Lorrayne Araujo Berlanda, Liana Costa Pereira Vilas Boas, Lídia Maria Pinto de Lima, Octávio Luiz Franco

引用次数: 0

Apelin is Peptide Increasing Tolerance of Organs and Cells to Hypoxia and Reoxygenation. The Signaling Mechanism 凋亡肽能增强器官和细胞对缺氧和再氧合的耐受性。信号机制

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-03-14 DOI: 10.1007/s10989-024-10599-6

Sergey Valentinovich Popov, Leonid Nikolaevich Maslov, Alexandr Valerievich Mukhomedzyanov, Maria Sirotina, Natalia Vladimirovna Naryzhnaya, Boris Konstantinovich Kurbatov, Alexandr Sergeevich Gorbunov, Michail Kilin, Viacheslav Nikolaevich Azev, Nirmal Singh, Feng Fu, Jian-Ming Pei

{"title":"Apelin is Peptide Increasing Tolerance of Organs and Cells to Hypoxia and Reoxygenation. The Signaling Mechanism","authors":"Sergey Valentinovich Popov, Leonid Nikolaevich Maslov, Alexandr Valerievich Mukhomedzyanov, Maria Sirotina, Natalia Vladimirovna Naryzhnaya, Boris Konstantinovich Kurbatov, Alexandr Sergeevich Gorbunov, Michail Kilin, Viacheslav Nikolaevich Azev, Nirmal Singh, Feng Fu, Jian-Ming Pei","doi":"10.1007/s10989-024-10599-6","DOIUrl":"https://doi.org/10.1007/s10989-024-10599-6","url":null,"abstract":"Over the last three decades, treatment of stroke and acute myocardial infarction (AMI) has been improved, but it has stagnated in the last few years. Patients with stroke and AMI are admitted with formed ischemic injury of the brain or the heart, thereby it is difficult to affect this injury. However, it was possible to affect reperfusion injury of the brain or the heart. Ischemic damage to the lung is observed in pulmonary embolism. Ischemia and reperfusion of kidneys are observed in kidney transplantation. Significant progress in an increase in the efficacy of kidney transplantation, in treatment of stroke, pulmonary embolism, and AMI can be achieved through the development of novel drugs capable of preventing reperfusion injury of the brain or the heart with high efficiency. Synthetic apelin analogues with a long half-life could be prototypes of such drugs. It was found that apelins can increase tolerance of the heart, the brain, the lung, and the intestine to ischemia/reperfusion (I/R). Protein kinases are involved in the neuroprotective, cardioprotective, renoprotective, and pulmonoprotective effects of apelins. Mitochondrial permeability transition pore and ATP-sensitive K+ channels are also involved in the protective effects of apelins. Apelins inhibit apoptosis and ferroptosis. Apelins activate autophagy of cardiomyocytes. Enzyme-resistant apelin analogues are perspective peptides for treatment of AMI, stroke, and I/R injury of lungs and kidneys.","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"83 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140148680","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

Evaluation of the Anti-biofilm Efficacy of Kyotorphin Derivatives and Biosafety Assessment: In Vitro and In Vivo Investigations Targeting Bacterial and Fungal Pathogens 京吗啡衍生物的抗生物膜功效评估与生物安全评价：针对细菌和真菌病原体的体外和体内研究

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-03-11 DOI: 10.1007/s10989-024-10598-7

Isabel Chaves Silva Carvalho, Fernanda da Silva Seiffert Simões, Vitor Martins de Andrade, Dayane Batista Tada, Montserrat Heras, Eduard Bardají, Mônica Lopes Ferreira, Miguel Augusto Rico Botas Castanho, Katia Conceição

{"title":"Evaluation of the Anti-biofilm Efficacy of Kyotorphin Derivatives and Biosafety Assessment: In Vitro and In Vivo Investigations Targeting Bacterial and Fungal Pathogens","authors":"Isabel Chaves Silva Carvalho, Fernanda da Silva Seiffert Simões, Vitor Martins de Andrade, Dayane Batista Tada, Montserrat Heras, Eduard Bardají, Mônica Lopes Ferreira, Miguel Augusto Rico Botas Castanho, Katia Conceição","doi":"10.1007/s10989-024-10598-7","DOIUrl":"https://doi.org/10.1007/s10989-024-10598-7","url":null,"abstract":"Kyotorphin (KTP) dipeptide (l-Tyrosine-l-Arginine) and their derivatives possess a multitude of functions, qualifying them as \"multifunctional peptides.\" Considering the escalating bacterial resistance to antibiotics, antimicrobial peptides offer a promising road, forming the central focus of this current investigation. The effectiveness of KTP derivatives, GABA-KTP-NH2 and Indol-KTP-NH2, were assessed for biofilm inhibition in bacterial and fungal strains. The viability of these derivatives was tested in fibroblasts and B16-F10-Nex2 cells. In vivo toxicity was evaluated using the model organisms Galleria mellonella and Danio rerio. Notably, both GABA-KTP-NH2 and Indol-KTP-NH2 derivatives effectively hindered biofilm formation in E. coli, S. pneumoniae, and C. krusei. In the G. mellonella model, the derivatives exhibited significant larval survival rates in toxicity tests, while in infection tests, they demonstrated efficient treatment against the evaluated microorganisms. Conversely, zebrafish assays revealed that Indol-KTP-NH2 induced substantial mortality rates in embryos after 72 and 96 h of exposure. Similarly, the GABA-KTP-NH2 derivative exhibited heightened lethality, noticeable at the 100 μM concentration after the same exposure periods. Importantly, toxicity assessments unveiled a relatively lower toxicity profile, coupled with a reduced potential for inducing abnormalities. These results highlight the necessity of employing a comprehensive approach that integrates diverse techniques to thoroughly assess toxicity implications.","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"33 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098913","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

π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands 参与妇科 Tankyrase-1 与抑制剂识别和结合的 π-堆叠相互作用：芳香族五肽配体合理设计的意义

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-03-10 DOI: 10.1007/s10989-024-10596-9

Yu Du, Lin Xu

{"title":"π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands","authors":"Yu Du, Lin Xu","doi":"10.1007/s10989-024-10596-9","DOIUrl":"https://doi.org/10.1007/s10989-024-10596-9","url":null,"abstract":"Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation.\u0000","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"90 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098908","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

Peptide Derivatives of Human and Rabbit Cathelicidin Reduce Inflammatory Cytokines in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients 人和兔类鞘氨醇多肽衍生物可降低类风湿性关节炎患者外周血单核细胞中的炎性细胞因子含量

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-03-05 DOI: 10.1007/s10989-024-10595-w

Marzieh Bashi, Rasoul Baharlou, Dariush Haghmorad, Raziyeh Lashkari, Bahman Yousefi, Hamid Madanchi

{"title":"Peptide Derivatives of Human and Rabbit Cathelicidin Reduce Inflammatory Cytokines in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients","authors":"Marzieh Bashi, Rasoul Baharlou, Dariush Haghmorad, Raziyeh Lashkari, Bahman Yousefi, Hamid Madanchi","doi":"10.1007/s10989-024-10595-w","DOIUrl":"https://doi.org/10.1007/s10989-024-10595-w","url":null,"abstract":"Peptides, as therapeutic agents, can mimic the actions of molecules involved in inflammatory disorders. Antimicrobial peptides (AMPs), generated by the innate immune system in all organisms, exhibit a broad spectrum of biological functionalities, including immunomodulation. The purpose of this study was to evaluate the effect of two modified peptide derivatives based on rabbit and human cathelicidin (nrCap18 and nhCap18) on the level of pro-inflammatory and anti-inflammatory cytokines in PBMCs of rheumatoid arthritis patients and healthy individuals in vitro. At first, peripheral blood samples were taken from seven rheumatoid arthritis patients and seven healthy individuals, and their PBMCs were isolated and cultured. Next, the toxicity of peptides was evaluated on PBMCs of these individuals, and the potential for hemolysis of these peptides on human blood erythrocytes was also calculated. After PBMCs were treated by peptide, cytokine level changes were investigated in the supernatants. These peptides showed low toxicity on PBMCs and human red blood cells. Also, these peptides could modulate and regulate cytokines in both patient/healthy groups. It is hoped that the effects of these peptides on cytokines modulation and regulation can open a new window for introducing an anti-inflammatory peptide. However, animal studies and clinical trials are needed to prove this claim.","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"51 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140032726","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

Therapeutic Peptides and Proteins: Stabilization Challenges and Biomedical Applications by Means of Nanodelivery Systems 治疗肽和蛋白质：纳米输送系统的稳定挑战和生物医学应用

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-02-28 DOI: 10.1007/s10989-024-10592-z

Elisa Berselli, Carlotta Coccolini, Giovanni Tosi, Evren H. Gökçe, M. Beatriz P. P. Oliveira, Faezeh Fathi, Karolline Krambeck, Eliana B. Souto

{"title":"Therapeutic Peptides and Proteins: Stabilization Challenges and Biomedical Applications by Means of Nanodelivery Systems","authors":"Elisa Berselli, Carlotta Coccolini, Giovanni Tosi, Evren H. Gökçe, M. Beatriz P. P. Oliveira, Faezeh Fathi, Karolline Krambeck, Eliana B. Souto","doi":"10.1007/s10989-024-10592-z","DOIUrl":"https://doi.org/10.1007/s10989-024-10592-z","url":null,"abstract":"The delivery of peptides and proteins usually faces formulation development challenges attributed to the difficulties encountered in their stabilization. Nanoparticles offer an alternative to improve the physicochemical stability of such biomacromolecules, while increasing their bioavailability by overcoming biological absorption barriers. With this review, we aim to discuss the stability problems of proteins and peptides that have driven the scientific community to find in nanotechnology a valid alternative for oral administration of biomolecules. In addition, we describe the most commonly used nanoparticles for this purpose (e.g., polymers such as polylactic acid, poly(lactic-co-glycolic acid), polycaprolactone, modified chitosan, and lipids such as oil-in-water nanoemulsions, self-emulsified drug delivery systems, solid lipid nanoparticles, nanostructured lipid carriers, liposomes, as well as hybrid systems like micelles), and we show some of the most important recent applications of these nanoparticles for the delivery of proteins and peptides, including for the treatment of diabetes, viruses (such as HIV), cancer, as well as in the development of vaccines.","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140004587","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

Investigating the Effects of Melittin-Loaded Pectin as Novel Anti Breast Cancer Drug to Increase the Apoptosis Rate 研究添加了美乐汀的果胶作为新型抗乳腺癌药物对提高细胞凋亡率的影响

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-02-28 DOI: 10.1007/s10989-024-10593-y

Esmaeil Alibeigi, Arsham Azari Dehkordi, Milad Asadian, Abbas Doosti, Tohid Piri-Gharaghie

{"title":"Investigating the Effects of Melittin-Loaded Pectin as Novel Anti Breast Cancer Drug to Increase the Apoptosis Rate","authors":"Esmaeil Alibeigi, Arsham Azari Dehkordi, Milad Asadian, Abbas Doosti, Tohid Piri-Gharaghie","doi":"10.1007/s10989-024-10593-y","DOIUrl":"https://doi.org/10.1007/s10989-024-10593-y","url":null,"abstract":"The peptide melittin is a promising possibility for cancer treatment. The present research evaluated the anticancer impact in vitro on breast cell lines using melittin, melittin-loaded pectin, and blank pectin. The “thin-layer hydration approach” was employed for generating the pectines; several melittin pectinal formulations were developed and studied in shape, size, polydispersity index, entrapment effectiveness, release kinetics, and stability. Breast cancer cells were tested using the hemolytic ability method, flow cytometry, the MTT test, the soft agar colony method, and wound healing analysis. The gene’s transcription was determined using real-time PCR (P < 0.05). Due to improved targeting, the effectiveness of encapsulation (83.57 ± 1.06), PDI (0.298 ± 0.65), and release percentage, as well as a significant anticancer impact on cell lines, this research demonstrated that melittin-loaded pectin is an adequate replacement in the treatment of breast cancer. The melittin-loaded pectin has a more significant impact on gene transcription in the examined cells than in other samples; it up-regulates the transcription of the Bax, P57, caspase3, and caspase9 genes while down-regulating the transcription of the MMP2, MMP2, and MMP9 genes (P < 0.05). In addition, compared to the melittin samples, they increased the apoptosis rate (by more than 40%) and hindered the invasion and migration of both cell lines. Our research has conclusively shown that melittin plasmid-loaded pectin has more anticancer properties than free melittin. This study has shown that pectins are appropriate vesicle transporters for melittin in contrast to the free form.","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"256 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010956","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

Evaluation of Anti-endotoxin Activity, Hemolytic Activity, and Cytotoxicity of a Novel Designed Peptide: An In Silico and In Vitro Study 评估一种新型设计肽的抗内毒素活性、溶血活性和细胞毒性：硅学和体外研究

IF 2.5 4区生物学

International Journal of Peptide Research and Therapeutics Pub Date : 2024-02-28 DOI: 10.1007/s10989-024-10591-0

Sadra Samavarchi Tehrani, Hamideh Mahmoodzadeh Hosseini, Seyed Ali Mirhosseini

{"title":"Evaluation of Anti-endotoxin Activity, Hemolytic Activity, and Cytotoxicity of a Novel Designed Peptide: An In Silico and In Vitro Study","authors":"Sadra Samavarchi Tehrani, Hamideh Mahmoodzadeh Hosseini, Seyed Ali Mirhosseini","doi":"10.1007/s10989-024-10591-0","DOIUrl":"https://doi.org/10.1007/s10989-024-10591-0","url":null,"abstract":"Endotoxin, also identified as lipopolysaccharide (LPS), is considered the pathogenic factor of septic shock triggered by Gram-negative bacteria and generates inflammatory responses. Synthetic peptides have attracted increasing attention from researchers for the blocking of LPS and treatment of sepsis. The aim of the study was to design a novel synthetic anti-endotoxin peptide and evaluate its effect in vitro. To design a new peptide, anti-endotoxin peptides were extracted from the APD3 site. The physicochemical features, secondary structure content, and tertiary structure type of each residue were determined by ProtParam, GOR IV, pep-fold, and I-TASSER. Hemolytic activity and cytotoxicity of the peptide on RAW264.7 cells were assessed by human RBC hemolysis test and MTT assay, respectively. Real-time PCR and western blot were used to evaluate the gene expression of IL-1β, TNF-α, IL-6, IL-10, iNOS, and TLR4, as well as the protein expression of NF-KB(P65), correspondingly. The designed peptide has 13 amino acid residues (GRRWWRFKKWWKF). The second structure of the peptide had 46.15% random coil and 53.85% extended strand. The results of the prediction of the tertiary structure demonstrated the peptide forms an alpha helix structure. It possesses low hemolytic activity and low cytotoxicity against RAW264.7 cells. This peptide remarkably restored LPS-induced TLR4 overexpression, and reduced gene expression of IL-1β, IL-6, iNOS, and TNF-α, whereas increased IL-10. This peptide significantly reduced the protein expression of NF-KB (P65). These findings imply that this peptide with low toxicity, hemolytic activity, and LPS-neutralizing activity merits more research as a possible anti-LPS agent for managing septic shock.","PeriodicalId":14217,"journal":{"name":"International Journal of Peptide Research and Therapeutics","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140004762","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