Seul Ki Yun, Seung Mok Yang, Moon Hwa Kwak, Jae Myung Park
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.
{"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}
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
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 in vitro antimicrobial effect of peptides with chitin binding properties isolated from Capsicum annuum seeds on the growth of the genus Candida. 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 Ca-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 Ca-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 Ca-Alb2S. Ca-F2 inhibited the growth of C. albicans and C. tropicalis, was not toxic to mammalian cells and still had a high survival rate when tested in vivo on Galleria mellonella larvae. This is the first report of chitin-binding peptides isolated from Capsicum 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.
{"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}
Nicholas A. Dalley, Kimberlee L. Stern, Richard R. Kitchen, Keegan B. Lloyd, Joshua L. Price
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 a, d, e, and g are understood in precise detail, conventional approaches often assume that the solvent-exposed b-, c-, and f-positions can be varied broadly for application-specific purposes with minimal consequences. However, a growing body of evidence suggests that interactions among these b, c, and f residues can contribute substantially to coiled-coil conformational stability. In the trimeric coiled coil described here, we find that b-position Glu10 engages in a stabilizing long-range synergistic interaction with c-position Lys18 (ΔΔΔGf = −0.65 ± 0.02 kcal/mol). This favorable interaction depends strongly on the presence of two nearby f-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 f-position Tyr14.
{"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><sub><i>f</i></sub> = −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}
Zhibin Yan, Guangyu Zhao, Qihao Lin, Guiping Zhuang, Jiayi Zhu, Juan Jin
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.
{"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}
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.
{"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}
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.
{"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}
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
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.
{"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}
Selene M. C. Cannelli, Ritvik Gupta, Tan Nguyen, Arunava Poddar, Srishti Sharma, Prachiti V. Vithole, Tony Z. Jia
Liquid–liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares compositional aspects of modern biological condensates and primitive LLPS is necessary. Here, we first focus on membraneless organelles composed of intrinsically disordered proteins (IDPs) and nucleic acids. Then, as a parallel, we explore primitive membraneless compartments composed of simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare composition of modern biological condensates and primitive phase‐separated compartments, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane‐bound cells. This review aims to provide a compositional comparison of modern and primitive phase‐separated structures in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed.
{"title":"A compositional view comparing modern biological condensates and primitive phase‐separated compartment","authors":"Selene M. C. Cannelli, Ritvik Gupta, Tan Nguyen, Arunava Poddar, Srishti Sharma, Prachiti V. Vithole, Tony Z. Jia","doi":"10.1002/pep2.24331","DOIUrl":"https://doi.org/10.1002/pep2.24331","url":null,"abstract":"Liquid–liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares compositional aspects of modern biological condensates and primitive LLPS is necessary. Here, we first focus on membraneless organelles composed of intrinsically disordered proteins (IDPs) and nucleic acids. Then, as a parallel, we explore primitive membraneless compartments composed of simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare composition of modern biological condensates and primitive phase‐separated compartments, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane‐bound cells. This review aims to provide a compositional comparison of modern and primitive phase‐separated structures in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44488885","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}
PASylation has been recently reported as a feasible alternative to PEGylation, which in essence is using polypeptides constituted of a combination of proline, alanine and serine for the hydrophilic modification of pharmaceuticals. In this work, we focused on the biocompatibility evaluation of two PAS peptides, (PAS)8 and (PA3)7 as well as the more frequently used polymers polyethylene glycol (PEG) and polyglycerol (PG). It has been verified in this study that (PAS)8 and (PA3)7 both exhibited low cell toxicity against HUVEC and RAW 264.7 cell lines. They also showed negligible RBC hemolysis and agglutination, which demonstrated adequate hemocompatibility. Their potential interactions with bovine serum albumin have also been investigated, and the results indicated little hydrophobic interactions between the polymers and protein. In conclusion, (PAS)8 and (PA3)7 as well as PEG and PG all showed considerable compatibility and safety in these studies, suggesting that (PAS)8 and (PA3)7 could be considered as potential candidates for PEG replacement in future studies.
{"title":"An in vitro evaluation of the biocompatibility of proline‐alanine‐serine peptides compared with polyethylene glycol and polyglycerol","authors":"Qianyu Zhang, Hongjing Chen, Huali Chen","doi":"10.1002/pep2.24330","DOIUrl":"https://doi.org/10.1002/pep2.24330","url":null,"abstract":"PASylation has been recently reported as a feasible alternative to PEGylation, which in essence is using polypeptides constituted of a combination of proline, alanine and serine for the hydrophilic modification of pharmaceuticals. In this work, we focused on the biocompatibility evaluation of two PAS peptides, (PAS)8 and (PA3)7 as well as the more frequently used polymers polyethylene glycol (PEG) and polyglycerol (PG). It has been verified in this study that (PAS)8 and (PA3)7 both exhibited low cell toxicity against HUVEC and RAW 264.7 cell lines. They also showed negligible RBC hemolysis and agglutination, which demonstrated adequate hemocompatibility. Their potential interactions with bovine serum albumin have also been investigated, and the results indicated little hydrophobic interactions between the polymers and protein. In conclusion, (PAS)8 and (PA3)7 as well as PEG and PG all showed considerable compatibility and safety in these studies, suggesting that (PAS)8 and (PA3)7 could be considered as potential candidates for PEG replacement in future studies.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44715586","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}
The scenario involving the alarming growth of bacterial resistance has never been more worrying. Increasingly selective and sophisticated bacterial strains resistant to traditional antibiotics are a threat to the health system worldwide. Therefore, antimicrobial peptides (AMPs) represent a promising path in the fight against multidrug‐resistant pathogens. Here, using an in silico methodology, employing robust software, the present study aims to analyze the chymo32 peptide, obtained by enzymatic fragmentation of the escapin protein to test its possible antibacterial effects, correlating them with their physical–chemical nature. In this study, we used in silico predictions such as structural prediction, physicochemical properties, hemolytic activity, and prediction of activity for immunomodulation. Among the 378 peptide fragments obtained from the original protein, chymo32 was the only peptide selected in the field of screenings involving sequence length, cationicity, hydrophobicity, and prediction of antibacterial activity. The physical–chemical properties of chymo32 are promising, as well as its prediction as AMP. The immunomodulation predictions showed no immunogenic potential, which indicates greater safety in the posterior steps in vitro, also highlighting the absence of hemolytic activity, one of the main problems associated with AMPs in the therapeutic clinic.
{"title":"Theoretical study of CHYMO32 peptide obtained by in silico fragmentation of the escapin protein isolated from marine hare Aplysia californica: A prediction for antimicrobial activity","authors":"Macley Silva Cardoso, J. M. Boeira","doi":"10.1002/pep2.24329","DOIUrl":"https://doi.org/10.1002/pep2.24329","url":null,"abstract":"The scenario involving the alarming growth of bacterial resistance has never been more worrying. Increasingly selective and sophisticated bacterial strains resistant to traditional antibiotics are a threat to the health system worldwide. Therefore, antimicrobial peptides (AMPs) represent a promising path in the fight against multidrug‐resistant pathogens. Here, using an in silico methodology, employing robust software, the present study aims to analyze the chymo32 peptide, obtained by enzymatic fragmentation of the escapin protein to test its possible antibacterial effects, correlating them with their physical–chemical nature. In this study, we used in silico predictions such as structural prediction, physicochemical properties, hemolytic activity, and prediction of activity for immunomodulation. Among the 378 peptide fragments obtained from the original protein, chymo32 was the only peptide selected in the field of screenings involving sequence length, cationicity, hydrophobicity, and prediction of antibacterial activity. The physical–chemical properties of chymo32 are promising, as well as its prediction as AMP. The immunomodulation predictions showed no immunogenic potential, which indicates greater safety in the posterior steps in vitro, also highlighting the absence of hemolytic activity, one of the main problems associated with AMPs in the therapeutic clinic.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49146729","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}
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