Journal of Peptide Science最新文献

{"title":"Synthesis and characterization of new antimicrobial peptides derived from Temporin F.","authors":"Lucas Melo Bosquetti, Cyntia Silva Oliveira, Giselle Cerchiaro, Vani Xavier Oliveira Junior","doi":"10.1002/psc.3655","DOIUrl":"https://doi.org/10.1002/psc.3655","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) are a promising source of new compounds against resistant bacteria. Temporins are a class of AMPs found on the amphibian Rana temporaria and show activity against Gram-positive and Gram-negative bacteria. There are few studies on how these antimicrobials have been used, but new Temporin-F derivatives were engineered with Lys-substitutions to assess the impact of the net charge on antimicrobial activity and toxicity. We demonstrated through some assays that it is possible to increase the antibacterial activity while maintaining a reduced peptide hemolytic activity with specific substitutions. Our lead synthetic peptide, G6K-Temporin F, has shown higher antimicrobial activity against Gram-negative and Gram-positive bacteria in vitro (MIC range 2 to 32 μmol L^-1), with low hemolytic activity maintained, resulting in an increase in the therapeutic window (TW), of 12.5. Also, it showed more resistant to enzymatic degradation. On the other hand, more significant increases in net charges, such as in P3K-G11K-Temporin F, result in a severe increase in toxicity with lower gains in antimicrobial activity (TW of 0.65). In conclusion, we demonstrated that a moderate increase in net charge can lead to a more active analog and G6K-Temporin F is revealed to be promising as a candidate for new AMP therapeutics.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365640","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":"RGD-functionalised self-assembling peptide hydrogel induces a proliferative profile in human osteoblasts in vitro.","authors":"Luis A Castillo-Díaz, Julie E Gough, Aline F Miller, Alberto Saiani","doi":"10.1002/psc.3653","DOIUrl":"https://doi.org/10.1002/psc.3653","url":null,"abstract":"<p><p>Self-assembling peptide hydrogels (SAPHs) have been used in the past decade as reliable three-dimensional (3D) synthetic scaffolds for the culture of a variety of mammalian cells in vitro. Thanks to their versatile physicochemical properties, they allow researchers to tailor the hydrogel properties, including stiffness and functionality to the targeted cells and cells' behaviour. One of the advantages of using SAPH scaffolds is the ease of functionalisation. In the present work, we discuss the effect that functionalising the FEFEFKFK (F, phenylalanine; K, lysine; and E, glutamic acid) hydrogel scaffold using the cell-binding RGDS (fibronectin - R, arginine; G, glycine; D, aspartic acid; S, serine) epitope affects the material properties as well as the function of encapsulated human osteoblast cells. RGDS functionalisation resulted in cells adopting an elongated morphology, suggesting attachment and increased proliferation. While this led to higher cell viability, it also resulted in a decrease in extra-cellular matrix (ECM) protein production as well as a decrease in calcium ion deposition, suggesting lower mineralisation capabilities. The work clearly shows that SAPHs are a flexible platform that allow the modification of scaffolds in a controlled manner to investigate cell-material interactions.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348959","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":"Combination of the amide‐to‐triazole substitution strategy with alternative structural modifications for the metabolic stabilization of tumor‐targeting, radiolabeled peptides","authors":"Xabier Guarrochena, Maximilian Anderla, Philipp Salomon, Irene V. J. Feiner, Berthold A. Nock, Theodosia Maina, Thomas L. Mindt","doi":"10.1002/psc.3654","DOIUrl":"https://doi.org/10.1002/psc.3654","url":null,"abstract":"Radiolabeled peptides play a key role in nuclear medicine to selectively deliver radionuclides to malignancies for diagnosis (imaging) and therapy. Yet, their efficiency is often compromised by low metabolic stability. The use of 1,4‐disubstituted 1,2,3‐triazoles (1,4‐Tzs) as stable amide bond bioisosteres can increase the half‐life of peptides in vivo while maintaining their biological properties. Previously, the amide‐to‐triazole substitution strategy was used for the stabilization of the pansomatostatin radioligand [<jats:sup>111</jats:sup>In]In‐AT2S, resulting in the mono‐triazolo‐peptidomimetic [<jats:sup>111</jats:sup>In]In‐XG1, a radiotracer with moderately enhanced stability in vivo and retained ability to bind multiple somatostatin receptor (SSTR) subtypes. However, inclusion of additional 1,4‐Tz led to a loss of affinity towards SST<jats:sub>2</jats:sub>R, the receptor overexpressed by most SSTR‐positive cancers. To enhance further the stability of [<jats:sup>111</jats:sup>In]In‐XG1, alternative modifications at the enzymatically labile position Thr<jats:sup>10</jats:sup>‐Phe<jats:sup>11</jats:sup> were employed. Three novel 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA)‐peptide conjugates were synthesized with a 1,4‐Tz (Asn<jats:sup>5</jats:sup>‐<jats:italic>Ψ</jats:italic>[Tz]‐Phe<jats:sup>6</jats:sup>) and either a β‐amino acid (β‐Phe<jats:sup>11</jats:sup>), reduced amide bond (Thr<jats:sup>10</jats:sup>‐<jats:italic>Ψ</jats:italic>[NH]‐Phe<jats:sup>11</jats:sup>), or N‐methylated amino acid (<jats:italic>N</jats:italic>‐Me‐Phe<jats:sup>11</jats:sup>). Two of the new peptidomimetics were more stable in blood plasma in vitro than [<jats:sup>111</jats:sup>In]In‐XG1. Yet none of them retained high affinity towards SST<jats:sub>2</jats:sub>R. We demonstrate for the first time the combination of the amide‐to‐triazole substitution strategy with alternative stabilization methods to improve the metabolic stability of tumor‐targeting peptides.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224468","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":"Multifunctional magneto-plasmonic lipogel based on peptide hydrogel for application in combined cancer therapy.","authors":"Valéria Gomes, Sérgio R S Veloso, André Carvalho, Loic Hilliou, Paulo J G Coutinho, Cacilda Moura, José A Martins, Elisabete M S Castanheira, Paula M T Ferreira","doi":"10.1002/psc.3650","DOIUrl":"https://doi.org/10.1002/psc.3650","url":null,"abstract":"<p><p>Supramolecular hydrogels, particularly low-molecular-weight peptide hydrogels, are promising drug delivery systems due to their ability to change the solubility, targeting, metabolism and toxicity of drugs. Magneto-plasmonic liposomes, in addition to being remotely controllable with the application of an external magnetic field, also increase the efficiency of encapsulated drug release through thermal stimulation, for example, with magnetic and optical hyperthermia. Thus, the combination of those two materials-giving magneto-plasmonic lipogels-brings together several functionalities, among which are hyperthermia and spatiotemporally controlled drug delivery. In this work, a novel dehydrodipeptide hydrogelator was synthesised, and the respective hydrogel was functionalized with magneto-plasmonic liposomes. After individually characterising the components with regard to their rheological, spectroscopic and magnetic properties, the magneto-plasmonic lipogel was equally characterised and evaluated concerning its ability to deliver drugs in a controlled fashion. To this end, the response of the 5(6)-carboxyfluorescein-loaded magneto-plasmonic lipogel to near-infrared light was assessed. The results showed that the system is a proper carrier of hydrophilic drugs and allows to envisage photo-responsive drug delivery. These facts, together with the magnetic guidance and hyperthermia capabilities of the developed composite gel, may pave the way to a new era in the treatment of cancer and other diseases.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046813","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":"Rational design of self-assembling ultrashort peptides for the shape- and size-tunable synthesis of metal nanostructures.","authors":"Urawadee Rajchakit, Hugh Douglas Glossop, Kelvin Wang, Jun Lu, Vijayalekshmi Sarojini","doi":"10.1002/psc.3651","DOIUrl":"https://doi.org/10.1002/psc.3651","url":null,"abstract":"<p><p>Peptides have attracted great interest as platforms for the design of nanocomposite hydrogels due to their distinct bioactivity, biofunctionality and biocompatibility. Previously, we have reported on a family of peptides that self-assembled to form stabilised three-dimensional hydrogel networks, displaying potent antimicrobial activity. In this paper, we report on the use of these hydrogelator sequences and their analogues as stabilisers and growth controllers to synthesise anisotropic gold nanoparticles (AuNPs) of different sizes and shapes. In particular, hollow spherical nanoparticles were obtained for HG2.81-AuNPs, whereas hexagonal nanoparticles were observed for TOH_1N-AuNPs and PentaOH-AuNPs in their respective hydrogel networks. The PentaOH-AuNPs' hydrogel exhibited excellent results with high antimicrobial potency against Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 and negligible cytotoxicity. On the other hand, TOH_1N-AuNPs showed no antibacterial activity and no cytotoxicity, demonstrating the versatility of these peptides. This work gives credence towards the development of these materials towards further applications such as in tissue culture technology and wound dressing materials.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036059","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 comprehensive study on the identification and characterization of major degradation products of synthetic liraglutide using liquid chromatography-high resolution mass spectrometry.","authors":"Devendra Badgujar, Sanket Bawake, Nitish Sharma","doi":"10.1002/psc.3652","DOIUrl":"https://doi.org/10.1002/psc.3652","url":null,"abstract":"<p><p>Liraglutide (LGT) is a synthetic glucagon-like peptide-1 analogue mainly used for the treatment of type-2 diabetes or obesity. Comprehensive stability testing is essential in the development and routine quality control of synthetic therapeutic peptide pharmaceuticals. The GLP-1 peptide drugs are usually formulated in aqueous-base solution, which can generate stability issues during manufacturing, storage or shipment. The current study endeavors to observe the chemical stability behavior of LGT by exposing the drug substance to oxidative and hydrolytic stress conditions. A simple liquid chromatography (LC) method was developed where sufficient resolution between LGT and the generated degradation products was achieved. In total, 19 degradation products (DPs) were separated under acidic, basic and oxidative stress conditions. Using LC-HRMS, MS/MS studies, the generated degradation products were identified and characterized. The mechanistic fragmentation pathway for all generated DPs were established and the plausible chemical structure for the identified DPs was predicted based on MS/MS data. The results strongly suggest that LGT is highly susceptible to degrade under oxidative and hydrolytic conditions. Furthermore, this study provides insights into the hydrolytic and oxidative stability of LGT, which can be implied during generic and novel formulation drug development and discovery in synthesizing relatively stable GLP-1 analogues.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004466","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 comprehensive guide for secondary structure and tertiary structure determination in peptides and proteins by circular dichroism spectrometer.","authors":"Akhilesh Kumar Kuril, Ankur Vashi, Praveen Kumar Subbappa","doi":"10.1002/psc.3648","DOIUrl":"https://doi.org/10.1002/psc.3648","url":null,"abstract":"<p><p>Secondary structure refers to highly regular local sub-structures formed by the polypeptide backbone through hydrogen bonding. The two main types of secondary structures are α-helices and β-strands (which can form β-sheets). The development of a robust circular dichroism (CD) method for structural analysis of biomolecules requires careful consideration of several key factors. Solvent selection plays a crucial role in maintaining the native or desired conformation of the sample while ensuring transparency in the relevant wavelength regions. Aqueous buffers are often preferred for studying proteins in their native state. Optimizing the sample concentration and path length is essential to achieve an optimal absorbance range and maximize the signal-to-noise ratio. Typical concentrations for far-UV CD measurements range from 0.1 to 1 mg/ml, with shorter path lengths (1 mm) allowing for higher concentrations and longer path lengths (5 mm) suitable for dilute solutions. Instrumental parameters, such as scanning speed, accumulations, and nitrogen flow rate, significantly impact the quality and reliability of the acquired CD spectra. Data processing is a critical step in obtaining accurate and interpretable CD spectra. Baseline correction, smoothing, and conversion to mean residue ellipticity are essential for reliable secondary structure analysis.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971334","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":"Uronium peptide coupling agents: Another case of occupational airborne allergic sensitization induced by HBTU.","authors":"Valentina Borghesani","doi":"10.1002/psc.3649","DOIUrl":"https://doi.org/10.1002/psc.3649","url":null,"abstract":"<p><p>Uronium peptide coupling agents (HBTU, HATU, and HCTU) create a special hazard as they are immune sensitizers. Few reported cases are mentioned in the literature; despite that, it is important to raise the awareness on the subject and to highlight the risk and potential symptoms that could occur to those who directly work in contact with uronium peptide coupling agents, as well as to the safety deputies in the universities and industries. Based on a personal experience, the health impact of laboratory exposure to HBTU is described, and the insights gained from the experience are developed. A skin irritation reaction and allergy symptoms induced by HBTU exposure are shown here as well as the rate of worsening of symptoms since the first allergic reaction. Recommendations for handling coupling agents more safely in the research laboratory will also be given, and a casuistry of the matter to help other lab-users to recognize, assess, minimize, prepare for emergencies (RAMP) process.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913055","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":"Coupling enterotoxigenic Escherichia coli heat-stable peptide toxin with 8-arm PEG enhances immunogenicity.","authors":"Ephrem Debebe Zegeye, Pooja Chaukimath, Yuleima Diaz, Sandhya S Visweswariah, Pål Puntervoll","doi":"10.1002/psc.3647","DOIUrl":"https://doi.org/10.1002/psc.3647","url":null,"abstract":"<p><p>Enterotoxigenic Escherichia coli (ETEC) strains, which produce the heat-stable enterotoxin (ST) either alone or in combination with the heat-labile enterotoxin, contribute to the bulk of the burden of child diarrheal disease in resource-limited countries and are associated with mortality. Developing an effective vaccine targeting ST presents challenges due to its potent enterotoxicity, non-immunogenicity, and the risk of autoimmune reaction stemming from its structural similarity to the human endogenous ligands, guanylin, and uroguanylin. This study aimed to assess a novel synthetic vaccine carrier platform employing a single chemical coupling step for making human ST (STh) immunogenic. Specifically, the method involved cross-linking STh to an 8-arm N-hydroxysuccinimide (NHS) ester-activated PEG cross-linker. A conjugate of STh with 8-arm structure was prepared, and its formation was confirmed through immunoblotting analysis. The impact of conjugation on STh epitopes was assessed using ELISAs with polyclonal and monoclonal antibodies targeting various epitopes of STh. Immunization of mice with the conjugate induced the production of anti-STh antibodies, exhibiting neutralizing activity against STh.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875186","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":"Au(I) complexes installed on a self-assembled peptide efficiently catalyze intramolecular cyclization reactions","authors":"Valentina Pirovano,&nbsp;Patrizia Brini,&nbsp;Elisa Brambilla,&nbsp;Maria Luisa Gelmi,&nbsp;Alessandra Romanelli","doi":"10.1002/psc.3630","DOIUrl":"10.1002/psc.3630","url":null,"abstract":"<p>Self-assembled peptides are used for diverse applications in the biomedical and technological fields. The morphology and function of the assembled systems are dictated by the peptide sequence and length. In this work, a supramolecular catalyst was obtained upon self-assembly of the diphenylalanine peptide conjugated to a triphenylphosphine Au(I) complex in acetonitrile. The assembled molecules were characterized by spectroscopic techniques and by scanning electron microscopy. The activity of the catalyst was tested on two substrates in cyclization reactions. The morphology and the dimensions of the assembled systems vary depending on the presence of a carboxyl versus an amide C-terminal end. The catalyst efficiently promotes intramolecular cyclization reactions. Results obtained encourage the use of self-assembled peptides for the obtainment of new and efficient catalysts.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468995","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}