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Targeting Peptide-Based Quorum Sensing Systems for the Treatment of Gram-Positive Bacterial Infections. 瞄准基于肽的法定人数感应系统治疗革兰氏阳性细菌感染。
IF 2.4 4区 生物学
Peptide Science Pub Date : 2023-03-01 Epub Date: 2022-11-12 DOI: 10.1002/pep2.24298
Tahmina A Milly, Yftah Tal-Gan
{"title":"Targeting Peptide-Based Quorum Sensing Systems for the Treatment of Gram-Positive Bacterial Infections.","authors":"Tahmina A Milly, Yftah Tal-Gan","doi":"10.1002/pep2.24298","DOIUrl":"10.1002/pep2.24298","url":null,"abstract":"<p><p>Bacteria utilize a cell density-dependent communication system called quorum sensing (QS) to coordinate group behaviors. In Gram-positive bacteria, QS involves the production of and response to auto-inducing peptide (AIP) signaling molecules to modulate group phenotypes, including pathogenicity. As such, this bacterial communication system has been identified as a potential therapeutic target against bacterial infections. More specifically, developing synthetic modulators derived from the native peptide signal paves a new way to selectively block the pathogenic behaviors associated with this signaling system. Moreover, rational design and development of potent synthetic peptide modulators allows in depth understanding of the molecular mechanisms that drive QS circuits in diverse bacterial species. Overall, studies aimed at understanding the role of QS in microbial social behavior could result in the accumulation of significant knowledge of microbial interactions, and consequently lead to the development of alternative therapeutic agents to treat bacterial infectivity. In this review, we discuss recent advances in the development of peptide-based modulators to target QS systems in Gram-positive pathogens, with a focus on evaluating the therapeutic potential associated with these bacterial signaling pathways.</p>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"115 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127943","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}
引用次数: 0
The manifold role of octapeptide repeats in prion protein assembly. 八肽重复序列在朊病毒蛋白组装中的多重作用。
IF 1.5 4区 生物学
Peptide Science Pub Date : 2023-03-01 Epub Date: 2023-01-30 DOI: 10.1002/pep2.24303
Amy H Guadagno, Scott H Medina
{"title":"The manifold role of octapeptide repeats in prion protein assembly.","authors":"Amy H Guadagno, Scott H Medina","doi":"10.1002/pep2.24303","DOIUrl":"10.1002/pep2.24303","url":null,"abstract":"<p><p>Prion protein misfolding is associated with fatal neurodegenerative disorders such as kuru, Creutzfeldt-Jakob disease, and several animal encephalopathies. While the C-terminal 106-126 peptide has been well studied for its role in prion replication and toxicity, the octapeptide repeat (OPR) sequence found within the N-terminal domain has been relatively under explored. Recent findings that the OPR has both local and long-range effects on prion protein folding and assembly, as well as its ability to bind and regulate transition metal homeostasis, highlights the important role this understudied region may have in prion pathologies. This review attempts to collate this knowledge to advance a deeper understanding on the varied physiologic and pathologic roles the prion OPR plays, and connect these findings to potential therapeutic modalities focused on OPR-metal binding. Continued study of the OPR will not only elucidate a more complete mechanistic model of prion pathology, but may enhance knowledge on other neurodegenerative processes underlying Alzheimer's, Parkinson's, and Huntington's diseases.</p>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"115 2","pages":""},"PeriodicalIF":1.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10162500/pdf/nihms-1871399.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9439671","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}
引用次数: 0
Chemical Shifts of Artificial Monomers Used to Construct Heterogeneous-Backbone Protein Mimetics in Random Coil and Folded States. 用于构建随机线圈和折叠状态下异质骨架蛋白模拟物的人工单体的化学位移。
IF 2.4 4区 生物学
Peptide Science Pub Date : 2023-03-01 Epub Date: 2022-11-12 DOI: 10.1002/pep2.24297
Shilpa R Rao, Thomas W Harmon, Shelby L Heath, Jacob A Wolfe, Jacqueline R Santhouse, Gregory L O'Brien, Alexis N Distefano, Zachary E Reinert, W Seth Horne
{"title":"Chemical Shifts of Artificial Monomers Used to Construct Heterogeneous-Backbone Protein Mimetics in Random Coil and Folded States.","authors":"Shilpa R Rao, Thomas W Harmon, Shelby L Heath, Jacob A Wolfe, Jacqueline R Santhouse, Gregory L O'Brien, Alexis N Distefano, Zachary E Reinert, W Seth Horne","doi":"10.1002/pep2.24297","DOIUrl":"10.1002/pep2.24297","url":null,"abstract":"<p><p>The construction of protein-sized synthetic chains that blend natural amino acids with artificial monomers to create so-called heterogeneous-backbones is a powerful approach to generate complex folds and functions from bio-inspired agents. A variety of techniques from structural biology commonly used to study natural proteins have been adapted to investigate folding in these entities. In NMR characterization of proteins, proton chemical shift is a straightforward to acquire, information-rich metric that bears directly on a variety of properties related to folding. Leveraging chemical shift to gain insight into folding requires a set of reference chemical shift values corresponding to each building block type (i.e., the 20 canonical amino acids in the case of natural proteins) in a random coil state and knowledge of systematic changes in chemical shift associated with particular folded conformations. Although well documented for natural proteins, these issues remain unexplored in the context of protein mimetics. Here, we report random coil chemical shift values for a library of artificial amino acid monomers frequently used to construct heterogeneous-backbone protein analogues as well as a spectroscopic signature associated with one monomer class, β<sup>3</sup>-residues bearing proteinogenic side chains, adopting a helical folded conformation. Collectively, these results will facilitate the continued utilization of NMR for the study of structure and dynamics in protein-like artificial backbones.</p>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"115 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127938","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}
引用次数: 0
Issue Information 问题信息
IF 2.4 4区 生物学
Peptide Science Pub Date : 2023-03-01 DOI: 10.1002/pep2.24274
{"title":"Issue Information","authors":"","doi":"10.1002/pep2.24274","DOIUrl":"https://doi.org/10.1002/pep2.24274","url":null,"abstract":"","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49627914","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}
引用次数: 0
Thermally‐controlled spherical peptide gel architectures prepared using the pH switch method 用pH开关法制备热控球形肽凝胶结构
IF 2.4 4区 生物学
Peptide Science Pub Date : 2023-02-22 DOI: 10.1002/pep2.24304
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}
引用次数: 1
Current Peptide Vaccine and Immunotherapy Approaches Against Alzheimer's Disease. 目前针对阿尔茨海默病的多肽疫苗和免疫疗法。
IF 1.5 4区 生物学
Peptide Science Pub Date : 2023-01-01 Epub Date: 2022-06-24 DOI: 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":1.5,"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}
引用次数: 0
Temperature‐induced structural change of integrin αvβ3 receptor and its interaction with the RGD peptide ligand 温度诱导的整合素αvβ3受体结构变化及其与RGD肽配体的相互作用
IF 2.4 4区 生物学
Peptide Science Pub Date : 2022-12-28 DOI: 10.1002/pep2.24302
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}
引用次数: 0
Effective cell penetration of negatively‐charged proline‐rich SAP(E) peptides with cysteine mutation 半胱氨酸突变的带负电荷富含脯氨酸的SAP(E)肽的有效细胞穿透
IF 2.4 4区 生物学
Peptide Science Pub Date : 2022-12-09 DOI: 10.1002/pep2.24301
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}
引用次数: 0
Issue Information 问题信息
IF 2.4 4区 生物学
Peptide Science Pub Date : 2022-11-01 DOI: 10.1002/pep2.24300
{"title":"Issue Information","authors":"","doi":"10.1002/pep2.24300","DOIUrl":"https://doi.org/10.1002/pep2.24300","url":null,"abstract":"","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":"44553172","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}
引用次数: 0
Mutagenesis of cyclotide Cter 27 exemplifies a robust folding strategy for bracelet cyclotides 环核苷酸Cter 27的突变是环核苷酸链折叠策略的一个例子
IF 2.4 4区 生物学
Peptide Science Pub Date : 2022-11-01 DOI: 10.1002/pep2.24284
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}
引用次数: 2
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