Peptide Science最新文献

{"title":"‘Main Mechanical Forces‐Chemical Interactions’ Interplay as a Tool to Elucidate Folding Mechanisms","authors":"Michele Larocca, Giuseppe Floresta, Daniele Verderese, Agostino Cilibrizzi","doi":"10.1002/pep2.24365","DOIUrl":"https://doi.org/10.1002/pep2.24365","url":null,"abstract":"The folding of peptides and proteins is rigidly reliant on the ‘chemical information’ carried by the specific amino acid sequence. In this study, three polypeptides (PDBs: 2jof, 1res and 1prv) were investigated as model systems to assess their folded features, thereby enabling further understanding of mechanisms that play a role in regulating the folding process more widely. A novel physico‐chemical approach of analysis is proposed herein, focusing on chemical interactions and their related mechanical forces that we trust are determinant to drive the folding. Through this methodology, we have predicted the conformations adopted by the three polypeptides and compared the outcomes to those experimentally determined, achieving a substantial structural agreement. Molecular dynamic simulations have been carried out to further support our calculations and structural results. Within the three models, we demonstrate that the interaction of each amino acid residue with its neighbour residues is a crucial determinant for the formation of the 3D stable native structures. This article provides initial evidence that the folding occurs by means of mechanical forces developed upon establishing chemical interactions amongst residues, which, in turn, are peculiar to each specific amino acid present in each position of the peptide chain.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"42 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141196726","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 Novel Method for Liraglutide Synthesis and Purification","authors":"Gabriela R. Barredo‐Vacchelli, Jésica A. Rodríguez, Joaquin A. Eloy, Silvia A. Camperi","doi":"10.1002/pep2.24351","DOIUrl":"https://doi.org/10.1002/pep2.24351","url":null,"abstract":"Liraglutide, developed by Novo Nordisk, is applied in Type 2 diabetes and obesity treatment. Several solid‐phase peptide synthesis protocols were designed for its production. However, current protocols are expensive and many of them are difficult to scale‐up. In this study, a novel alternative for liraglutide production was developed. The peptide was elongated by Fmoc/tBu solid‐phase peptide synthesis on 4‐hydroxymethylbenzoyl–ChemMatrix (HMBA‐CM) resin using the chaotropic agent LiCl as an additive to prevent peptide aggregation. After elongation, removal of side‐chain protecting groups and peptide cleavage from the resin was performed by a two‐stage procedure. Side‐chain protecting groups were removed with 92.5% TFA, leaving the unprotected peptide attached to the solid support. The resin was thoroughly washed to eliminate the contaminants. Next, peptide release was achieved by treating the peptidyl resin with NaOH 0.1 N. This two‐stage procedure assures a high‐purity product without the need of using a large amount of ether as in previous protocols. Finally, liraglutide was purified by hydrophobic interaction with low‐pressure liquid chromatography (HI‐LPLC) instead of using the expensive RP‐HPLC applied in reported methods. This simple and economic method resulted in a high yield and a purity product while overcoming the high cost and difficulties of current processes.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"116 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836504","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":"Molecular Dynamics and Binding Energetics of Fluspirilene With BACE1: Implications for Alzheimer's Disease Intervention","authors":"Kunal Bhattacharya, Atanu Bhattacharjee, Manodeep Chakraborty, Dibyajyoti Das","doi":"10.1002/pep2.24349","DOIUrl":"https://doi.org/10.1002/pep2.24349","url":null,"abstract":"Alzheimer's disease (AD) is a serious neurodegenerative disorder that results in cognitive deterioration, amnesia, and alterations in behavior, rendering it a significant issue in public health. The pathogenesis involves amyloid plaques highlighting the importance of targeting BACE1. This study explores fluspirilene, a di‐phenyl‐butyl‐piperidine as a potential BACE1 inhibitor for AD treatment. Fluspirilene was analyzed for ADMET. In silico molecular docking assessed fluspirilene's binding affinity with BACE1. Re‐docking a co‐crystallized ligand confirmed the docking process. Molecular dynamics simulations and related multifaceted computational analyses were conducted to assess the stability of docked complexes. Fluspirilene had good physicochemical and pharmacokinetic characteristics according to ADMET profiling. In silico molecular docking showed multiple BACE1 interactions with a binding affinity of −9.2 kcal/mol and fluspirilene–BACE1 complex stability was confirmed by molecular dynamics simulation results. Possible therapeutic applications in lowering Aβ generation and treating AD are indicated by the compound's pharmacokinetics, molecular interactions, and binding energetics. Validation and optimization of experiments are necessary for the clinical development of fluspirilene as a BACE1 inhibitor for AD.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"35 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140572981","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 and Molecular Simulation of Antimicrobial Peptide Variants From Lactobacillus sp. Against Porphyromonas gingivalis and Fusobacterium nucleatum in Oral Squamous Cell Carcinoma","authors":"Zarin Taj, Indranil Chattopadhyay","doi":"10.1002/pep2.24348","DOIUrl":"https://doi.org/10.1002/pep2.24348","url":null,"abstract":"<jats:italic>Porphyromonas gingivalis</jats:italic> and <jats:italic>Fusobacterium nucleatum</jats:italic> are known to contribute to a variety of tumorigenic pathways linked to the progression of oral squamous cell carcinoma (OSCC). The growing global incidence of antibiotic resistance highlights the critical need to consider the use of antimicrobial peptides (AMPs) as a viable alternative to conventional antibiotics. The current study comprehensively tested <jats:italic>Lactobacillus</jats:italic> sp.−derived AMPs against bacterially exacerbated OSCC. A total of 52 AMPs were obtained from various databases, and an in silico analysis determined their potent antibacterial and anticancer characteristics after a rigorous screening and pruning approach. Twelve AMPs were tested for 3D structural alignment prediction and validation, with the GH12 synthetic AMP serving as a control. These candidate peptides were thoroughly screened against six important virulence proteins of <jats:italic>P. gingivalis</jats:italic> and four of <jats:italic>F. nucleatum</jats:italic>, with the lowest energy score of the docked complexes measuring binding affinity and interactions with active residues being chosen. plpl_18 was determined as the most efficient new AMP that interacted with the virulence protein RagB of <jats:italic>P. gingivalis</jats:italic> and Fap2 of <jats:italic>F. nucleatum</jats:italic> with docking scores of −238.24 and −254.27 kcal/mol, respectively. This AMP plpl_18 was docked against selective target OSCC regulatory proteins such as cytokines, metallomatrix proteinase, MAPK, E‐cadherin, and JAK‐1 proteins. Among these proteins, it docked against matrix metalloproteinase‐9 with the highest negative docking scores of −7.5, −260.956, and −1361.9 kcal/mol using AutoDock Vina, HPEPDOCK, and ClusPro 2.0, respectively. Molecular dynamic simulation was used to perform extrapolated validation. These computational studies provide an essential foundation for anticipated laboratory and clinical investigations concerning the possibility of adapting therapeutic peptides based on probiotics to combat the proliferation of OSCC, which is accelerated by <jats:italic>F. nucleatum</jats:italic> and <jats:italic>P. gingivalis</jats:italic>.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"59 Pt A 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140074690","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":"Oligopeptides analysis in spiderhawk's venom (Pepsis decorata Perty, 1833, Hymenoptera: Pompilidae)","authors":"Matheus Nolasco, Douglas O. C. Mariano, Daniel C. Pimenta, Humberto Fonseca de Freitas, Samuel Silva da Rocha Pita, Alexsandro Branco","doi":"10.1002/pep2.24347","DOIUrl":"https://doi.org/10.1002/pep2.24347","url":null,"abstract":"Wasps have been neglected in toxinological studies, even with their diversity of species, when compared to other groups of venomous animals such as snakes, scorpions, and spiders. Solitary wasps, such as <i>Pepsis decorata</i>, are known for their mechanism of total or temporary paralysis of the host. In addition, their venoms are considered sources for studies of small peptides, bioactive peptides with neural and antimicrobial activities. In this work, some oligopeptides were analyzed by de novo sequencing identifying 39 oligopeptide sequences. Some sequences were similar to proctolin, a bradykinin-potentiating peptide, and poneritoxin, one bradykinin-related peptide. As proctolin-like peptides were the major constituent in distinct experimental conditions, it was selected for further in silico studies in order to understand its possible importance as a constituent of wasp venom and whether these peptides could be of biotechnological importance. We investigate its binding mode comparing with proctolin and we further analyzed the importance of the tyrosine-leucine-glutamic acid (YLE) tripeptide-motif conservation. This experimental, an in silico approach, increased the range of compounds identified in peptide analyses proving good characterization of little-known peptidic compounds.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"12 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139769841","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":"Review on therapeutic potential of peptides: Advancements in synthesis methods, linear and cyclic peptides, and strategies for overcoming challenges","authors":"Naurin Lalani, Sunil Tivari, Vicky Jain, Yashwantsinh Jadeja","doi":"10.1002/pep2.24343","DOIUrl":"https://doi.org/10.1002/pep2.24343","url":null,"abstract":"In the realm of therapeutic peptides, tremendous progress has been achieved in the last two decades. The building block of peptides that is, ‘Amino Acid’ has been modified by various chemical modifications such as side-chain alteration in linear peptides, cyclization, back-bone modification, pro-drug moiety, conjugation with heterocycles, and natural products to make peptides a foremost candidate as a therapeutic drug. Since the advent of insulin in 1922, peptides have immensely affected the development of the pharmaceutical industry giving rise to the peptide-based drug industry. In recent years, peptides having antimicrobial, antiviral, anti-tumor, anti-inflammatory, anti-aging, and antioxidant properties have developed. Also, it has now entered as a potent candidate in the field of oncology and also become a valuable tool as a radiolabeled peptide for the detection of various diseases. Generally, peptides were extracted from natural sources in the olden days, but presently work is directed towards finding alternate and sustainable ways for developing synthetic peptides. The present review covers the discussion about the historic evaluation of peptides, available effective synthetic processes, current advancements, use of bioinformatic tools, computational strategies, and the methodology to overcome the barrier for making peptides the potent candidate for the future world.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"13 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666748","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":"Oral delivery of the amylin receptor agonist pramlintide","authors":"Celimar Sinézia, Tháyna Sisnande, Luis Peña Icart, Luís Maurício T. R. Lima","doi":"10.1002/pep2.24346","DOIUrl":"https://doi.org/10.1002/pep2.24346","url":null,"abstract":"Amylin receptor agonism safely benefit diabetic patients, reducing the insulin requirements and glycemic excursions. Pramlintide is the triple proline human amylin analogue first used as injectable drug, but lacking physico-chemical compatibility when co-formulated with insulin. Here, we report the design and characterization of polymeric microparticles for oral delivery of pramlintide. Eudragit S100, a gastric-resistant polymer, was used in preparation of pramlintide-loaded spherical microcapsules by double emulsion and solvent evaporation technique, with approximately 66 μm ± 11 particle size, with 83.2% ± 2.7 efficiency for pramlintide entrapment and 67.6% ± 2.1 yield. Intra-venous pramlintide free in solution showed a plasmatic half-life of 6.8 min in mice. In contrast, oral delivery of acid-resistant pramlintide-loaded microparticles in mice showed a protracted release for 120 min compared to 30 min obtained for pramlintide in solution. Our data provide evidences for the potential use of the oral route in the therapeutic development of pramlintide formulations.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"50 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139656258","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":"Network pharmacology combined with molecular docking simulations reveal the mechanism of action of Glycyrrhiza for treating pneumonia","authors":"Dongxin Yang, Zhehong Li, Yongrui Peng, Xiaofeng Zhu, Jun Gong, Cuilian Chen","doi":"10.1002/pep2.24342","DOIUrl":"https://doi.org/10.1002/pep2.24342","url":null,"abstract":"A well-established mechanism of action for managing pneumonia using <i>Glycyrrhiza</i> is unknown. Using network pharmacology and molecular docking simulations, we investigated the mechanism of action of <i>Glycyrrhiza</i> against pneumonia. To identify the targets of the active components of <i>Glycyrrhiza</i> from the Traditional Chinese Medicine Systems Pharmacology database, oral bioavailability and drug likeness were utilized as indicators. Pneumonia-associated genes were identified and screened from the databases. Integrated analysis was conducted to elucidate the relationship between the active components of <i>Glycyrrhiza</i> and intersecting genes; a comprehensive <i>Glycyrrhiza</i> active component-target gene relationship map was constructed. Intersecting genes underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to examine their biological functions. A protein–protein interaction network map was constructed to identify hub genes. Molecular docking simulations were performed to investigate binding interactions between hub genes and their corresponding active components. Of the 96 overlapping genes, topological analysis revealed 10 hub genes. <i>Glycyrrhiza</i> exerts therapeutic effects through a multi-target and multipathway approach, suggesting a synergistic treatment for pneumonia. MAPK14 showed a favorable binding affinity with most of the active compounds, indicating that MAPK14 and related compounds in <i>Glycyrrhiza</i> have development potential.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"47 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139496065","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":"Molecular mechanism study and potential active ingredients prediction of Danhe granules in the treatment of hypercholesterolemia via TICE","authors":"Cong Shibo, Yu Tong, Wang Sili, Gu Shuxiao, Qiao Yanfang, Liu Susu, Gao Pan, Meng Jingke, Chai Xinlou","doi":"10.1002/pep2.24345","DOIUrl":"https://doi.org/10.1002/pep2.24345","url":null,"abstract":"This study aims to explore the molecular mechanism and potential active ingredients of Danhe granules in improving the blood lipid level of hypercholesterolemia by intestinal TICE (transintestinal cholesterol excretion) through in vivo experimental research, network pharmacology methods, and molecular docking. The diet-induced hypercholesterolemia rat model evaluated the effects of Danhe granules on fecal cholesterol levels and intestinal TICE-related protein expression in rats. Based on the experimental results, the network pharmacology method was used to predict the potential active ingredients, and the binding strength between the potential active ingredients and key targets was further confirmed by molecular docking. Danhe granules increased LDLR, ABCG5, ABCB1, and LXRα which can promote the uptake of cholesterol by intestinal cells and the excretion of cholesterol into the intestine, and then reduce the levels of serum LDL-C and TC and increase the level of fecal TC, so as to achieve the effect of treating hypercholesterolemia. The results of network pharmacology and molecular docking showed that 19 active ingredients had good binding activity with the targets. These may be the active ingredients of Danhe granules for the treatment of hypercholesterolemia. This study revealed the molecular mechanism of Danhe granules in the treatment of hypercholesterolemia via TICE, and preliminarily clarified the potential effective ingredients. It provides new ideas for the treatment of hypercholesterolemia and the development of new drugs.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"51 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139459578","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":"Investigation of commercially available resins for the automated flow synthesis of difficult or long peptide sequences","authors":"Michael A. Lee, Joseph S. Brown, Andrei Loas, Bradley L. Pentelute","doi":"10.1002/pep2.24344","DOIUrl":"https://doi.org/10.1002/pep2.24344","url":null,"abstract":"Solid-phase peptide synthesis (SPPS) is widely used to produce peptides. Since its invention, the solid support has enabled the elongation of the synthetic peptide chain. As technologies have evolved, the length of peptide chains accessible with SPPS has grown to that of single-domain proteins. Resins for SPPS have advanced to improve synthesis capabilities as well. The functionalization of solid supports with polyethylene glycol (PEG) is commonly employed in a range of commercially available resins to aid in the ability to synthesize long or difficult sequences. A notable example of a widely used PEG-based solid support is ChemMatrix® resin; however, this and several similar resins have recently been discontinued. Here, we demonstrate and compare the capabilities of OctaGel™, ProTide®, and TentaGel XV® resins in synthesizing sequences ranging from peptides to single domain proteins using automated fast-flow peptide synthesis. Our studies indicate that each resin performs well for routine peptide synthesis by automated flow, whereas TentaGel XV resin showed the best performance for synthesis of difficult or long peptide sequences when comparing quality using yield, purity, and real-time UV absorbance monitoring during synthesis.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"87 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139459828","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}