Peptide Science最新文献

{"title":"PL‐101‐WK, a novel tryptophan‐ and lysine‐rich peptide with antimicrobial activity against Staphylococcus aureus","authors":"Parvin Zadeh Shahraki, P. Farrokh","doi":"10.1002/pep2.24296","DOIUrl":"https://doi.org/10.1002/pep2.24296","url":null,"abstract":"Designing short antimicrobial peptides (AMPs), which are active against drug‐resistant bacteria, is a promising way to find new therapeutic agents. In this research, a novel short AMP, PL‐101‐WK, was designed based on PL‐101 (a derivative of plicatamide). Here, the substitution of Phe and His with Trp and Lys was considered. The antimicrobial activity and physicochemical properties of PL‐101‐WK were compared with PL‐101 by in silico analysis. The antimicrobial activity in the presence or absence of NaCl concentration, thermal stability, hemolytic activity, and selectivity of the peptides were determined. By substitution of Lys and Trp residues, positive charge, in vitro stability, and hydrophilicity of PL‐101‐WK were raised compared to the template. PL‐101‐WK had the best minimum inhibitory concentration (MIC) value of 64 μg/ml against Staphylococcus aureus strains, which showed at least 16‐fold reduction when compared to the values of PL‐101. The MICs of PL‐101‐WK were retained toward S. aureus strains at physiological salt concentration. While PL‐101‐WK did not display acceptable thermal stability, it had desirable selectivity against bacteria. The maximum hemolytic activity of PL‐101‐WK was 1.65% at 512 μg/ml. Taken together, increasing positive charge and the presence of Trp residues were enhanced the potential of antibacterial activity of PL‐101.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46542752","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 Shelf Stable Fmoc Hydrazine Resin for the Synthesis of Peptide Hydrazides.","authors":"Michael J Bird, Philip E Dawson","doi":"10.1002/pep2.24268","DOIUrl":"10.1002/pep2.24268","url":null,"abstract":"<p><p>C-terminal hydrazides are an important class of synthetic peptides with an ever expanding scope of applications, but their widespread application for chemical protein synthesis has been hampered due to the lack of stable resin linkers for synthesis of longer and more challenging peptide hydrazide fragments. We present a practical method for the regeneration, loading, and storage of trityl-chloride resins for the production of hydrazide containing peptides, leveraging 9-fluorenylmethyl carbazate. We show that these resins are extremely stable under several common resin storage conditions. The application of these resins to solid phase peptide synthesis (SPPS) is demonstrated through the synthesis of the 40-mer GLP-1R agonist peptide \"P5\". These studies support the broad utility of Fmoc-NHNH-Trt resins for SPPS of C-terminal hydrazide peptides.</p>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"114 5","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10504959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linearized teixobactin is inactive and after sequence enhancement, kills methicillin-resistant Staphylococcus aureus via a different mechanism.","authors":"Qianhui Wu, Biswajit Mishra, Guangshun Wang","doi":"10.1002/pep2.24269","DOIUrl":"10.1002/pep2.24269","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> is a highly adaptable pathogen that can rapidly develop resistance to conventional antibiotics such as penicillin. Recently, teixobactin was discovered from uncultivated soil bacteria by using the i-chip technology. This depsipeptide forms an ester bond between the backbone C-terminal isoleucine carboxylic acid and the hydroxyl group of threonine at position 8. Also, it contains multiple nonstandard amino acids, making it costly to synthesize. This study reports new peptides designed by linearizing teixobactin. After linearization and conversion to normal amino acids, teixobactin lost its antibacterial activity. Using this inactive template, a series of peptides were designed via hydrophobic patching and residue replacements. Three out of the five peptides were active. YZ105, only active against Gram-positive bacteria, however, showed the highest cell selectivity index. Different from teixobactin, which inhibits cell wall synthesis, YZ105 targeted the membranes of methicillin-resistant <i>S. aureus</i> (MRSA) based on kinetic killing, membrane permeation, depolarization, and scanning electron microscopy studies. Moreover, YZ105 could kill nafcillin-resistant MRSA, Staphylococcal clinical strains, and disrupted preformed biofilms. Taken together, YZ105, with a simpler sequence, is a promising lead for developing novel anti-MRSA agents.</p>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"114 5","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/fd/PEP2-114-e24269.PMC9564113.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10452235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structured cyclic peptide mimics by chemical ligation","authors":"B. C. Atkinson, A. Thomson","doi":"10.1002/pep2.24266","DOIUrl":"https://doi.org/10.1002/pep2.24266","url":null,"abstract":"We report the development of a β‐turn mimic that allows the direct formation of cyclic peptides through a spontaneous cyclisation under standard solid phase peptide synthesis (SPPS) cleavage conditions. The mimic is formed via an acylhydrazone, which is either reduced in situ by triisopropylsilane‐trifluoroacetic acid, or which can be isolated and reduced in a separate step. This method uses commercially available reagents and is compatible with manual and automated SPPS methods. The cyclisation is tolerant of polar residues at the C‐terminal position, with the exception of asparagine, for which a subsequent structural rearrangement similar to aspartimide formation was observed. The cyclisation method has been shown to tolerate ring sizes equivalent to 5–10 amino acid residues. We have used this method to design and synthesise potential selective integrin binding sequences with controlled conformations.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46180199","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":"Synoeca‐MP: New insights into its mechanism of action by using NMR and molecular dynamics simulations approach","authors":"E. Alves, Bruno de Paula Oliveira de Santos, L. Rodrigues, Carlos Daniel Pereira Freitas, Lucianna Helene Silva dos Santos, S. C. Dias, O. Franco, L. Lião, M. D. de Magalhães","doi":"10.1002/pep2.24293","DOIUrl":"https://doi.org/10.1002/pep2.24293","url":null,"abstract":"Synoeca‐MP is a 14‐residue amidated peptide, belongs to the mastoparan family and it is found in the venom of the wasp Synoeca surinama and has antibacterial and antifungal activity. The low cytotoxicity of the peptide also makes it an excellent candidate for drug development. To better understand its selectivity and interaction with the membrane, the peptide behavior in membrane‐like environments was studied here and the peptide structure in SDS micelles was determined by NMR spectroscopy. The behavior of the peptide in hydrophobic media and in different pH ranges was studied by CD spectroscopy. The incorporation of residues into the anionic micelles was studied by hydrogen‐deuterium exchange. The peptide stability and insertion in the micelles was studied by molecular dynamics simulations. Synoeca‐MP, bound to SDS micelles, exhibits a partial α‐helix conformation, with the first five residues and the last two unfolded. H/D exchange showed that the peptide has a slow exchange rate. After 164 h, four residues had not yet completed H/D substitution, suggesting parallel alignment of the peptide with the micelle, mainly due to the hydrophobic interface. This may indicate a carpet interaction model of the peptide with micelles. The molecular simulation study of peptide showed that the peptide consists of a well‐folded alpha‐helix core and unfolded extremities, which are responsible for the nature of the peptide interaction. The biophysical analyses can improve the atomic understanding of the mode of action of the peptide and help in future improvements of the peptide for clinical usage.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42522137","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":"Advances in the use of plants as potential biofactories in the production of antimicrobial peptides","authors":"Cristiane dos Santos, O. Franco","doi":"10.1002/pep2.24290","DOIUrl":"https://doi.org/10.1002/pep2.24290","url":null,"abstract":"Plants subjected to phytopathogens can synthesize peptides with antimicrobial properties. In the last few decades, there has been an impressive increase in the prospection of antimicrobial peptides (AMPs) due to continuous demand for the development and manufacture of new antibiotics. In this setting, plants have attracted scientific and pharmaceutical interest and are considered promising AMPs biofactories. However, it is a great challenge to explore the diversity of actions needed to obtain a pharmaceutical product with AMPs derived from plants on a large scale. This review presents the last 5 years main findings on plants used as AMPs biofactories. Published works in this period were reviewed, and perspectives are presented on recombinant AMPs for drug production that appear in a plant‐based system, as well as products available on the market.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"115 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41468275","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":"Issue Information","authors":"","doi":"10.1002/pep2.24292","DOIUrl":"https://doi.org/10.1002/pep2.24292","url":null,"abstract":"","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47339385","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":"Facile synthetic method for peptoids bearing multiple azoles on side chains","authors":"Yen Jea Lee, Soyeon Park, Yujeong Kim, S. H. Kim, Jiwon Seo","doi":"10.1002/pep2.24287","DOIUrl":"https://doi.org/10.1002/pep2.24287","url":null,"abstract":"Natural metalloenzymes stabilize metal centers by utilizing multiple imidazole moieties. Inspired by nature's design principles, the introduction of multiple azoles into ligands has been an effective method for constructing transition metal complexes. Herein, we describe a post‐synthetic modification of peptoids to incorporate multiple azoles on side chains. A simple substitution reaction between an azole (imidazole, pyrazole, 1,2,3‐triazole, and tetrazole) and a chloroalkyl‐containing peptoid provided access to a variety of azole‐containing peptoids. Ten azole‐containing peptoids were synthesized from a single chloroalkyl‐containing peptoid, and the efficiency of each azole for the substitution reaction was evaluated. We have identified that several of the azole‐containing peptoids are capable of binding with Cu(II) and Fe(III). Our synthetic approach can contribute to the expansion of peptoids' chemical diversity and the development of novel peptoids for metal recognition and catalysis.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45423853","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":"Parallel arrangement of peptides appended to a rigid, bimetallic, constrained ring system","authors":"T. Curran, A. Marrone, Lauren M. Davidson, Niranjana Pokharel, J. Frempong, I. Tolbatov, M. L. Phillip, Cosmic B. Gober, Haoyu Yang, J. Stewart","doi":"10.1002/pep2.24286","DOIUrl":"https://doi.org/10.1002/pep2.24286","url":null,"abstract":"Cyclic tungsten bis‐alkyne complexes derived from a 1,1′‐ferrocenyldialkyne (1 and 2) adopt a rigid conformation where the two alkynes are in a syn orientation and are likely positioned about 3.5 Å apart. Since intramolecular hydrogen bonding in protein secondary structures positions the donors and acceptors 3.3 Å apart, it is proposed that linking two peptides to the two alkynes in one of these complexes might be a way to generate a model system for generating peptide β‐sheets. To explore this question, a series of peptide derivatives of 1 were prepared. Attachment of peptides to the bimetallic ring system was achieved by reaction of peptide derivatives of 4‐iodobenzoic acid or 4‐iodoaniline with 1 via a Sonogashira coupling. Subsequent reaction of these dialkynes with W(CO)3(dmtc)2 (dmtc = dimethylditiocarbamate) afforded the desired cyclic tungsten bis‐alkyne complexes as a 1:1 mixture of diastereomers. The two diastereomers were not separable using typical chromatographic methods (TLC, HPLC and flash chromatography); however, their presence and relative amounts could be detected and measured in the 1H NMR spectra. The conformations of these peptide derivatives of 1 were examined using NMR and DFT methods. It was found that appending the peptides to the two alkynes did not alter the rigid conformation of the ferrocene‐tungsten bis‐alkyne ring system found in 1; the ring system remained rigid and retained the intramolecular hydrogen bond across the bimetallic ring system. Whether the amide and urethane NH protons in these complexes are involved in intramolecular hydrogen bonds was explored using a DMSO titration experiment and computational methods. Data from the DMSO titrations showed that there was only one robust intramolecular hydrogen bond, the hydrogen bond across the bimetallic ring; the other amide and urethane NH protons were accessible to the solvent. The DFT calculations showed the peptides attached to the bimetallic ring system can adopt a number of different orientations having similar energies, and that some of these conformations include cross‐strand hydrogen bonds. The data indicate that appending peptides to the bimetallic ring system via the two alkynes produces molecules where the two peptides are held in a parallel arrangement.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"114 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51336580","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":"Synthesis and biological evaluation of cilengitide derivatives on TGF‐β1‐induced epithelial‐to‐mesenchymal transition in human non‐small cell lung cancer cells","authors":"Kyeong‐Yong Park, Jisu Jeong, Jiyeon Kim","doi":"10.1002/pep2.24285","DOIUrl":"https://doi.org/10.1002/pep2.24285","url":null,"abstract":"Epithelial‐to‐mesenchymal transition (EMT) is an important process leading to invasiveness of cancer cells and poor prognosis in non‐small cell lung cancer (NSCLC) progression. Cilengitide (cyclo[RGDf(NMe)V]), a cyclic RGD pentapeptide, has been shown to enhance the inhibitory effect of epidermal growth factor receptor (EGFR) inhibitors on TGF‐β1‐induced mesenchymal marker expression and invasion by NSCLC A549 cells. In this study, we synthesized cilengitide and derivatives and evaluated their biological effects on TGF‐β1‐induced EMT phenotype marker expression and invasion in human NSCLC cells. Among the synthesized derivatives, R‐1 (cRGDwV) and R‐7 (cRGDyV) were found to be the most effective in inhibiting the growth of NSCLC cells. These cilengitide derivatives showed an inhibitory effect on the TGF‐β1‐induced EMT process and invasion through inhibition of Smad or non‐Smad signaling pathways in NSCLC A549 cells. Through this study, we demonstrated that cilengitide derivatives containing the RGD sequence and hydrophobic amino acids, such as cilengitide, exhibit inhibitory effects on NSCLC cell growth and EMT inhibition. In addition, the potential of these peptides as a drug that can be used to inhibit metastasis of various cancers accompanying the EMT process was suggested.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"19 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41265956","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}