Peptide Science最新文献

{"title":"A strategy for producing isotopically labeled peptides with antimicrobial activity or with short in vivo lifetime in Escherichia coli","authors":"Qiongqiong Ren, Zejun Fan, Rong Han, Meihui Sang, Changxing Ma, Xiaoli Zhao, Shenlin Wang","doi":"10.1002/pep2.24340","DOIUrl":"https://doi.org/10.1002/pep2.24340","url":null,"abstract":"Engineered <i>Escherichia coli</i> (<i>E. coli</i>) strains have been widely used to produce isotopically labeled peptides for NMR characterization on their structures and interactions. However, production of antimicrobial peptides (AMPs) by <i>E. coli</i> is still challenging, because AMPs are toxic to <i>E. coli</i> host and would lead to cell death after induction. On the other hand, expression of short peptides in <i>E. coli</i> host often encounter problems of the short in vivo lifetime of the peptides, which were rapidly degraded by endogenous enzymes during expression and purification steps. This report presents a practical method for overcoming these bottlenecks to enable <i>E. coli</i> to express AMPs and peptides that have short in vivo lifetime. This design uses the fusion of thioredoxin tags at both the N- and C-termini of the target peptides. The steric effect of the large soluble tags at both ends of the peptide reduces peptide accessibility, thereby enhancing their in vivo stability and eliminating the toxicity associated with AMPs. The approach was validated using an AMP A3K/L7K-LAH4 (K3K7) and a membrane fusion peptide (FP), which is a segment of the spike protein of SARS-CoV-2 and functions in fusing viral membranes and host cell membranes. Fusion expression of K3K7 with a thioredoxin tag only at the N-terminal resulted in high toxicity to the host cells, leading to impaired cell growth and a failure to obtain expressed fusion protein. In contrast, the fusion proteins from both termini were successfully expressed and purified. In the case of the FP, the fusion of thioredoxin at both termini significantly enhanced its stability, protecting it from enzymatic degradation during expression and purification steps. On the contrary, the FP with thioredoxin fused only at the N-terminal was found to be unstable in <i>E. coli</i> host strains. As stable isotope labeling on peptide is essentially important in NMR-based structure and interaction studies, we also demonstrated that the developed approach enables efficient ¹⁵N labeling for NMR studies. This strategy may also be extended to produce other challenging peptides.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"16 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139459579","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":"In silico prediction of preventive activities of bioactive hazelnut peptides against COVID‐19 and Monkeypox 2022","authors":"Zeynep Saliha Güneş, B. Cakir, İbrahim Gülseren","doi":"10.1002/pep2.24341","DOIUrl":"https://doi.org/10.1002/pep2.24341","url":null,"abstract":"The coronavirus 2 (SARS‐CoV‐2), a positive‐sense RNA virus that causes severe acute respiratory illness, is the cause of Coronavirus Disease 2019 (COVID‐19) and Monkeypox is a zoonotic viral disease caused by a double‐strand enveloped DNA virus, a member of the Poxviridae family under the umbrella of the Orthopoxvirus genus. These viruses have harmed global health, societal stability, and global economy prompting the development of new therapeutic options. The purpose of this study was to analyze the potency of hazelnut‐derived bioactive peptides for usage in preventive measures against SARS‐CoV‐2 and Monkeypox infections. Since SARS‐CoV‐2 entry into the host cell takes place through angiotensin‐converting enzyme (ACE) receptors, an in silico attempt was made here to analyze the previously characterized ACE‐inhibitory hazelnut peptides for their anti‐COVID potential. First of all, peptide sequences with PeptideRanker values >0.5 were determined, where 43 of 256 hazelnut peptides met this condition. BIOPEP tools were used to calculate their ACE‐inhibitory characteristics. VPHW and DENPRHF demonstrated the strongest ACE‐inhibitory activity based on BIOPEP analysis. The binding potentials of VPHW (p < 0.001) and DENPRHF (p < 0.001) peptides to ACE were statistically significant based on PepSite2 analysis. The hazelnut‐derived peptides were docked with ACE, spike proteins, SARS‐CoV‐2 proteases, host cell receptors, and Monkeypox 2022 membrane proteins using HPEPDOCK and CABS‐dock. The in silico findings pointed out potential inhibition of SARS‐CoV‐2 main protease in the host cell and Monkeypox 2022 membrane protein and demonstration of multiple bioactivities.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"1 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139439501","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":"Crystal structures reveal that the sterically hindered pivaloyl-cisProlyl amide bond is energetically frustrated","authors":"Shreya Banerjee, Sunil K. Gupta, Sunit Pal, Erode N. Prabhakaran","doi":"10.1002/pep2.24337","DOIUrl":"https://doi.org/10.1002/pep2.24337","url":null,"abstract":"CisPro/transPro isomerism at the prolyl amide bond is a fundamental dynamism governing protein folding, structure, and functions. Since cisPro crystal structures are rare, the interactions influencing their structures are less understood, unlike transPro. Crystal data for the sterically hindered pivaloyl-cisProlyl amide bond (2,2-dimethyl-1-(1-pyrrolidinyl)-1-propanone, Piv-cisPro) were particularly lacking for decades. Here we introduce Piv-Pro-Xaa-OMe dipeptides which crystallize with the elusive Piv-cisPro (Xaa is Leu/Ile) and the abundant Piv-transPro (Xaa is Gly/Phe) conformers.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"3 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139398069","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":"Development and validation of cyclic peptide probe for gastric cancer based on phage display technique","authors":"Seul Ki Yun, Seung Mok Yang, Moon Hwa Kwak, Jae Myung Park","doi":"10.1002/pep2.24339","DOIUrl":"https://doi.org/10.1002/pep2.24339","url":null,"abstract":"Cancer-targeting diagnostics should have a sensitive and specific binding affinity. To achieve this, biomarker development is critical. This study aimed to develop and validate a 7-mer cyclic peptide probe that can target gastric cancer. We developed this probe based on LGR5 (leucine-rich repeat-containing G-protein coupled receptor 5)-specific targeting, which is a marker for gastric cancer stem cells. An LGR5 targeting peptide sequence that was developed using phage display technology resulted in a cyclic peptide, C-YLASRVH-C (named YLA). We conjugated this peptide with fluorescent probes to validate its specific targeting ability for gastric cancer. The fluorescence-labeled YLA peptide exhibited 3.0-fold higher fluorescence intensity in a gastric cancer cell line (MKN45) than it did in a normal cell line (CCD841 cells). In contrast, pancreatic and colorectal cancer cells did not show significant fluorescence intensity with the YLA peptide. To verify its tumor-targeting affinity, we developed a control peptide, C-YLASAVH-C (named YLASA) using an ALA scanning experiment. Whole-body imaging of a gastric cancer xenograft model showed higher fluorescence intensity of tumors in the YLA peptide group than in the control peptide group. Moreover, ex vivo imaging of tumor tissues exhibited 6.8-fold higher fluorescence intensity in the YLA peptide group compared to that in the YLASA control peptide group. In conclusion, we confirmed that the YLA peptide probe functions as a specific diagnostic probe for gastric cancer. We anticipate that it will play a theranostic role through further development.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"23 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139094506","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":"Chitin-binding peptides from Capsicum annuum with antifungal activity and low toxicity to mammalian cells and Galleria mellonella larvae","authors":"Gabriella Rodrigues Gonçalves, Marciele Souza Silva, Layrana Azevedo dos Santos, Larissa Maximiniano Resende, Gabriel Bonan Taveira, Thomas Zacarone Afonso Guimarães, Sarah Rodrigues Ferreira, Antonia Elenir Amancio Oliveira, Celso Shiniti Nagano, Renata Pinheiro Chaves, André de Oliveira Carvalho, Rosana Rodrigues, Olney Vieira da Motta, Valdirene Moreira Gomes","doi":"10.1002/pep2.24338","DOIUrl":"https://doi.org/10.1002/pep2.24338","url":null,"abstract":"In recent years, there have been several reports of the presence of toxic proteins in cultivated or wild plant species, which are implicated in plant defense mechanisms. The existence of these proteins raises the possibility of biotechnological applications originating from the development of new techniques to combat diseases caused by fungi. In this context, there are chitin-binding proteins. Chitin is an essential component of the fungal cell wall, so chitin-binding proteins are important in controlling fungal growth. Thus, the objective of this study was to characterize and evaluate the <i>in vitro</i> antimicrobial effect of peptides with chitin binding properties isolated from <i>Capsicum annuum</i> seeds on the growth of the genus <i>Candida</i>. Initially, proteins were extracted in phosphate pH 5.4, and a chitin column was equilibrated with sodium acetate (0.08 M, pH 4.5), where 50 mg of the peptide-rich heated fraction from each species was applied. Subsequently, the retained material was eluted with 0.1 M HCl. Tricine SDS–PAGE was used to visualize the peptides. After chromatography, two fractions, F1 (not retained in the chitin column) and F2 (retained in the chitin column, named <i>Ca</i>-F2), were obtained. Electrophoresis showed major protein bands between 3 and 14 kDa. Electrophoresis from chitin affinity chromatography also showed major bands between 3 and 14 kDa, especially for <i>Ca</i>-F2 retained in the column. One peptide obtained from the F2 fraction was identified by mass spectrometry and showed similarity to seed 2S albumin, named <i>Ca</i>-Alb2S. <i>Ca</i>-F2 inhibited the growth of <i>C. albicans</i> and <i>C. tropicalis</i>, was not toxic to mammalian cells and still had a high survival rate when tested in vivo on <i>Galleria mellonella</i> larvae. This is the first report of chitin-binding peptides isolated from <i>Capsicum</i> seeds through an affinity column and their biological activities. These studies are at an early stage; therefore, other tests are needed to study the mechanism of action of the fraction, since the findings indicate great potential for the development of new antifungal molecules.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"131 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139094503","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":"Electrostatic origin of a stabilizing synergistic interaction among b-, c-, and f-residues in a trimeric coiled coil","authors":"Nicholas A. Dalley, Kimberlee L. Stern, Richard R. Kitchen, Keegan B. Lloyd, Joshua L. Price","doi":"10.1002/pep2.24336","DOIUrl":"https://doi.org/10.1002/pep2.24336","url":null,"abstract":"Coiled coils are one of most common protein quaternary structures and represent the best understood relationship between amino acid sequence and protein conformation. Whereas the roles of residues at the canonical heptad positions the <i>a</i>, <i>d</i>, <i>e</i>, and <i>g</i> are understood in precise detail, conventional approaches often assume that the solvent-exposed <i>b</i>-, <i>c</i>-, and <i>f</i>-positions can be varied broadly for application-specific purposes with minimal consequences. However, a growing body of evidence suggests that interactions among these <i>b</i>, <i>c</i>, and <i>f</i> residues can contribute substantially to coiled-coil conformational stability. In the trimeric coiled coil described here, we find that <i>b</i>-position Glu10 engages in a stabilizing long-range synergistic interaction with <i>c</i>-position Lys18 (ΔΔΔ<i>G</i>_<i>f</i> = −0.65 ± 0.02 kcal/mol). This favorable interaction depends strongly on the presence of two nearby <i>f</i>-position residues: Lys 7 and Tyr14. Extensive mutational analysis of these residues in the presence of added salt versus denaturant suggests that this long-range synergistic interaction is primarily electrostatic in origin, but also depends on the precise location and acidity of a side-chain hydrogen-bond donor within <i>f</i>-position Tyr14.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"16 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518134","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 network pharmacology approach to explore the molecular mechanism of active peptide ingredients of <i>Carapax Trionycis</i> on liver fibrosis","authors":"Zhibin Yan, Guangyu Zhao, Qihao Lin, Guiping Zhuang, Jiayi Zhu, Juan Jin","doi":"10.1002/pep2.24335","DOIUrl":"https://doi.org/10.1002/pep2.24335","url":null,"abstract":"Abstract Carapax Trionycis is a traditional Chinese medicine and it has been clear that oligo‐peptides from Carapax Trionycis extract (CTP) are the main active substances for the treatment of liver diseases. However, little is known about the mechanism of CTP against liver fibrosis. Here, network pharmacology combined with molecular docking were performed to identify the in‐silico molecular mechanism and the potential targets for CTP to ameliorate liver fibrosis. We collected eight active peptides ingredients that published in public databases and predicted the targets. Liver fibrosis related genes were acquired from the GeneCards and DisGeNET platform. Then, we identified a total of 52 peptides‐liver fibrosis‐related genes. KEGG and GO enrichment analyses indicated that these targets are significantly enriched in relaxin signaling pathway, IL‐17 signaling pathway, TNF signaling pathway. We identified the top 10 genes with high centrality measures from the network by CytoHubba, including CASP3, AKT1, IL1B, MMP9, and PTGS2. The molecular docking between these hub genes and the corresponding CTP was performed in GRAMM and visualized by PyMOL. Our results provide an important reference and scientific basis for treating liver fibrosis with CTP.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135779743","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":"Investigating the interaction of azobenzene moiety on the aromatic amino acid tryptophan","authors":"Charnette Frederic, Gregory R. Wiedman","doi":"10.1002/pep2.24334","DOIUrl":"https://doi.org/10.1002/pep2.24334","url":null,"abstract":"Abstract Azobenzenes are a series of compounds that can be isomerized upon irradiation with light. These molecules can modify the physical, chemical, and biological properties of a diverse range of materials. They can control protein structure and function with temporal and spatial precision. In this work, we investigated the possible interaction between azobenzene and aromatic amino acids. We hypothesized that aromatic amino acids, such as tryptophan, would show altered photochemical properties when conjugated with azobenzene. When irradiated at either 365 nm or 465 nm, the molecule now lacks the usually characteristic photoswitch capabilities and is visibly fluorescent at 365 nm. To our knowledge, this is the first evidence to suggest that primary protein structure could affect photoswitch activity. The knowledge gained from this research will help to further the understanding of azobenzenes as they are used in biomolecules.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135855065","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":"Bioactive peptides against angiotensin‐converting enzyme I: An <scp><i>in silico</i></scp> study","authors":"Antistio Alvíz‐Amador, Neyder Contreras‐Puentes, Johana Márquez‐Lázaro","doi":"10.1002/pep2.24332","DOIUrl":"https://doi.org/10.1002/pep2.24332","url":null,"abstract":"Abstract Bioactive peptides are currently emerging as nonpharmacological alternatives for treating noncommunicable diseases, including hypertension. Pharmacological treatments for hypertension typically involve angiotensin I converting enzyme inhibitors such as Captopril and enalapril. This study aimed to evaluate the activity of bioactive peptides derived from food sources against this enzyme and show its possible mechanism of inhibitory action. A comprehensive search was conducted in peptide databases to identify peptides with antihypertensive properties. Subsequently, docking studies, simulations, and predictive tests assessing ADME parameters, intestinal stability, and allergenicity were performed using bioinformatics tools. The docking and simulation results demonstrated that PEP2 exhibited superior ACE1 inhibitory potential compared to other peptides, even though it had lower human intestinal absorption. In conclusion, this study suggests that these peptides hold promising potential as nutraceuticals for hypertension treatment.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135965982","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":"Generation and study of antibodies against two triangular trimers derived from Aβ","authors":"Adam G. Kreutzer, Ryan J. Malonis, Chelsea Marie T. Parrocha, Karen Tong, Gretchen Guaglianone, Jennifer T. Nguyen, Michelle N. Diab, Jonathan R. Lai, James S. Nowick","doi":"10.1002/pep2.24333","DOIUrl":"https://doi.org/10.1002/pep2.24333","url":null,"abstract":"Abstract Monoclonal antibodies (mAbs) that target the β‐amyloid peptide (Aβ) are important Alzheimer's disease research tools and are now being used as Alzheimer's disease therapies. Conformation‐specific mAbs that target oligomeric and fibrillar Aβ assemblies are of particular interest, as these assemblies are associated with Alzheimer's disease pathogenesis and progression. This article reports the generation of rabbit mAbs against two different triangular trimers derived from Aβ. These antibodies are the first mAbs generated against Aβ oligomer mimics in which the high‐resolution structures of the oligomers are known. We describe the isolation of the mAbs using single B‐cell sorting of peripheral blood mononuclear cells (PBMCs) from immunized rabbits, the selectivity of the mAbs for the triangular trimers, the immunoreactivity of the mAbs with aggregated Aβ 42 , and the immunoreactivity of the mAbs in brain tissue from the 5xFAD Alzheimer's disease mouse model. The characterization of these mAbs against structurally defined trimers derived from Aβ enhances understanding of antibody‐amyloid recognition and may benefit the development of diagnostics and immunotherapies in Alzheimer's disease.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135155463","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}