Sawsan Almohammed, M. Kanoun, S. Goumri‐Said, M. Alam, Agata Fularz, Abdullah Alnaim, J. Rice, B. Rodriguez
{"title":"Thermally‐controlled spherical peptide gel architectures prepared using the pH switch method","authors":"Sawsan Almohammed, M. Kanoun, S. Goumri‐Said, M. Alam, Agata Fularz, Abdullah Alnaim, J. Rice, B. Rodriguez","doi":"10.1002/pep2.24304","DOIUrl":"https://doi.org/10.1002/pep2.24304","url":null,"abstract":"Self‐assembling nanostructured peptide gels are promising materials for sensing, drug delivery, and energy harvesting. Of particular interest are short diphenylalanine (FF) peptides modified with 9‐fluorenylmethyloxycarbonyl (Fmoc), which promotes the association of the peptide building blocks. Fmoc‐FF gels generally form fibrous networks and while other structures have been demonstrated, further control of the gelation and resulting ordered three‐dimensional structures potentially offers new possibilities in tissue engineering, sensing, and drug release applications. Herein, we report that the structure tunability of Fmoc‐FF gels can be achieved by controlling the water content and the temperature. We further explore the incorporation of metal nanoparticles in the formation of the gel to enable optical sensing applications based on hybrid Fmoc‐FF‐nanoparticle microspheres. Finally, fluorescence lifetime imaging microscopy reveals a correlation between lifetime and reduced bandgap, in support of a semiconductor‐induced charge transfer mechanism that might also increase the stability of an excited state of a probe molecule. The observations potentially further widen the use of these peptide materials in bioimaging and sensing applications.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48688180","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}
Peptide SciencePub Date : 2023-01-01Epub Date: 2022-06-24DOI: 10.1002/pep2.24289
Chelsea Marie T Parrocha, James S Nowick
{"title":"Current Peptide Vaccine and Immunotherapy Approaches Against Alzheimer's Disease.","authors":"Chelsea Marie T Parrocha, James S Nowick","doi":"10.1002/pep2.24289","DOIUrl":"10.1002/pep2.24289","url":null,"abstract":"<p><p>Peptide vaccines and immunotherapies against aggregating proteins involved in the pathogenesis and progression of Alzheimer's disease (AD) - the β-amyloid peptide (Aβ) and tau - are promising therapeutic avenues against AD. Two decades of effort has led to the controversial FDA approval of the monoclonal antibody Aducanumab (Aduhelm), which has subsequentially sparked the revival and expedited review of promising monoclonal antibody immunotherapies that target Aβ. In this review, we explore the development of Aβ and tau peptide vaccines and immunotherapies with monoclonal antibodies in clinical trials against AD.</p>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"115 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9636401","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}
Anqi Wang, Kai Yue, Yiang Wei, Weishen Zhong, Genpei Zhang
{"title":"Temperature‐induced structural change of integrin αvβ3 receptor and its interaction with the RGD peptide ligand","authors":"Anqi Wang, Kai Yue, Yiang Wei, Weishen Zhong, Genpei Zhang","doi":"10.1002/pep2.24302","DOIUrl":"https://doi.org/10.1002/pep2.24302","url":null,"abstract":"The structural change of receptor protein at high temperatures is one of the factors affecting the targeting ability of ligand‐installed nanocarriers for combined therapy of hyperthermia and drug delivery. In this study, the binding behaviors and mechanisms of integrin αvβ3 receptor and the arginine‐glycine‐aspartic acid (RGD) peptide ligand at high temperatures were investigated both theoretically and experimentally. The structural parameters of integrin αvβ3 at different temperatures and the interaction forces between the RGD peptide and integrin αvβ3 at different binding sites were calculated by molecular dynamics simulation. Fourier transform infrared spectroscopy, energy dispersive spectroscopy, ultraviolet–visible absorption spectroscopy, and atomic force microscopy were used to analyze the structural changes of integrin αvβ3 and to measure the ligand‐receptor interaction. Results show that the number of hydrogen bonds decreased and the secondary structure of integrin αvβ3 changed with the increase in temperature, indicating the denaturation of integrin αvβ3. The structural stability of the integrin αv subunit was better than that of the integrin β3 subunit at high temperatures. The interaction between the RGD peptide and integrin αvβ3 weakened as the temperature increased because the structure of the integrin αvβ3 binding site became more flexible and the corresponding calcium ions were shed from the binding site. The strongest interaction force was exhibited at the binding site of the integrin β3 subunit at 310 K while it was found at the binding site of the integrin αv subunit at higher temperatures, owing to the smaller structure deformation of the integrin αv subunit.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48178199","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}
Sewon Lim, Jinhyuk Park, Seung‐Eun Chong, Sungwhan Kim, Yoonhwa Choi, Sohee Nam, Yan Lee
{"title":"Effective cell penetration of negatively‐charged proline‐rich SAP(E) peptides with cysteine mutation","authors":"Sewon Lim, Jinhyuk Park, Seung‐Eun Chong, Sungwhan Kim, Yoonhwa Choi, Sohee Nam, Yan Lee","doi":"10.1002/pep2.24301","DOIUrl":"https://doi.org/10.1002/pep2.24301","url":null,"abstract":"Most of cell penetrating peptides (CPPs) are rich in positively‐charged amino acids but the cationic property may provoke possible problems in practical applications. In this study, we carefully substituted the hydrophobic amino acids in the SAP(E) sequence, a rare example of negatively‐charged proline‐rich CPP, with cysteine for enhancement of cell penetrating activity as well as reversible conjugation of cargo molecules. Most substituents showed almost negligible cell penetrating activity, but a cysteine substituent on the 7th valine (SAP(E)‐7C) showed more improved cell penetrating activity than SAP(E). When treated to cells, the negatively‐charged SAP(E)‐7C exhibited much lower degree of co‐localization with acidic endosomes or lysosomes compared to positively‐charged TAT. SAP(E)‐7C could significantly enhance the PTX efficacy on MDA‐MB‐231 cells by non‐covalent complexation with PTX. As a proof‐of‐concept for covalent conjugation of cargo drugs, mercaptoethanol, a model drug, was conjugated to the cysteine residue of SAP(E)‐7C via a disulfide bond, and the glutathione‐dependent release from the conjugate was confirmed. The negatively‐charged SAP(E)‐7C with a cysteine handle can be a useful molecular module for the development of CPP‐based drug delivery carrier.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49375714","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}
Tien T. Dang, P. Harvey, L. Y. Chan, Yen‐Hua Huang, Q. Kaas, D. Craik
{"title":"Mutagenesis of cyclotide Cter 27 exemplifies a robust folding strategy for bracelet cyclotides","authors":"Tien T. Dang, P. Harvey, L. Y. Chan, Yen‐Hua Huang, Q. Kaas, D. Craik","doi":"10.1002/pep2.24284","DOIUrl":"https://doi.org/10.1002/pep2.24284","url":null,"abstract":"In contrast to Möbius and trypsin inhibitor cyclotides, members of the bracelet subfamily are typically intractable to chemical synthesis and folding. In a significant advance in the field, the bracelet cyclotides ribe 33 and Cter 27 were successfully produced synthetically in moderate yield in a recent study. That synthetic method was a breakthrough as members of the bracelet subfamily of cyclotides had hitherto eluded attempts to be synthetically produced, apart from one report of cyO2 production in which a complicated folding strategy was used. In the current study the successful in vitro folding of three mutants of bracelet cyclotide Cter 27 is reported. This study broadens our understanding of the folding of bracelet cyclotides and elucidates the three dimensional structure of synthetic Cter 27, providing a new class of cyclotide molecular grafting scaffold for drug design applications.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41905384","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":"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}
Peptide SciencePub Date : 2022-09-01Epub Date: 2022-04-16DOI: 10.1002/pep2.24268
Michael J Bird, Philip E Dawson
{"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}
Peptide SciencePub Date : 2022-09-01Epub Date: 2022-04-25DOI: 10.1002/pep2.24269
Qianhui Wu, Biswajit Mishra, Guangshun Wang
{"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}