Bianca M. Nastri, Annalisa Chianese, Rosa Giugliano, Laura Di Clemente, Carla Capasso, Alessandra Monti, Nunzianna Doti, Valentina Iovane, Serena Montagnaro, Ugo Pagnini, Giuseppe Iovane, Carla Zannella, Anna De Filippis, Massimiliano Galdiero
{"title":"Oreoch-1: A broad-spectrum virus and host-targeting peptide against animal infections","authors":"Bianca M. Nastri, Annalisa Chianese, Rosa Giugliano, Laura Di Clemente, Carla Capasso, Alessandra Monti, Nunzianna Doti, Valentina Iovane, Serena Montagnaro, Ugo Pagnini, Giuseppe Iovane, Carla Zannella, Anna De Filippis, Massimiliano Galdiero","doi":"10.1002/psc.3593","DOIUrl":"10.1002/psc.3593","url":null,"abstract":"<p>In recent decades, the global rise of viral emerging infectious diseases has posed a substantial threat to both human and animal health worldwide. The rapid spread and accumulation of mutations into viruses, and the limited availability of antiviral drugs and vaccines, stress the urgent need for alternative therapeutic strategies. Antimicrobial peptides (AMPs) derived from natural sources present a promising avenue due to their specificity and effectiveness against a broad spectrum of pathogens. The present study focuses on investigating the antiviral potential of oreochromicin-1 (oreoch-1), a fish-derived AMP obtained from Nile tilapia, against a wide panel of animal viruses including canine distemper virus (CDV), Schmallenberg virus (SBV), caprine herpesvirus 1 (CpHV-1), and bovine herpesvirus 1 (BoHV-1). Oreoch-1 exhibited a strong antiviral effect, demonstrating an inhibition of infection at concentrations in the micromolar range. The mechanism of action involves the interference with viral entry into host cells and a direct interaction between oreoch-1 and the viral envelope. In addition, we observed that the peptide could also interact with the cell during the CDV infection. These findings not only highlight the efficacy of oreoch-1 in inhibiting viral infection but also emphasize the potential of fish-derived peptides, specifically oreoch-1, as effective antiviral agents against viral infections affecting animals, whose potential to spill into humans is high. This research contributes valuable insights to the ongoing quest for novel antiviral drugs with the potential to mitigate the impact of infectious diseases on a global scale.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110457","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}
Tim Pasch, Nicole Bäumer, Sebastian Bäumer, Frank Buchholz, Henning D. Mootz
{"title":"Towards targeted Cas9 (CRISPR-Cas) delivery: Preparation of IgG antibody-Cas9 conjugates using a split intein","authors":"Tim Pasch, Nicole Bäumer, Sebastian Bäumer, Frank Buchholz, Henning D. Mootz","doi":"10.1002/psc.3592","DOIUrl":"10.1002/psc.3592","url":null,"abstract":"<p>The CRISPR-Cas9 system has revolutionized the field of genetic engineering, but targeted cellular delivery remains a central problem. The delivery of the preformed ribonuclease-protein (RNP) complex has the advantages of fewer side effects and avoidance of potential permanent effects. We reasoned that an internalizing IgG antibody as a targeting device could address the delivery of Cas9-RNP. We opted for protein <i>trans</i>-splicing mediated by a split intein to facilitate posttranslational conjugation of the two large protein entities. We recently described the cysteine-less CL split intein that efficiently performs under oxidizing conditions and does not interfere with disulfide bonds or thiol bioconjugation chemistries. Using the CL split intein, we report for the first time the ligation of monoclonal IgG antibody precursors, expressed in mammalian cells, and a Cas9 precursor, obtained from bacterial expression. A purified IgG-Cas9 conjugate was loaded with sgRNA to form the active RNP complex and introduced a double-strand break in its target DNA in vitro. Furthermore, a synthetic peptide variant of the short N-terminal split intein precursor proved useful for chemical modification of Cas9. The split intein ligation procedure reported here for IgG-Cas9 provides the first step towards a novel CRISPR-Cas9 targeting approach involving the preformed RNP complex.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049728","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":"Isolation and antioxidant activity of peptides from Chinese hairy tofu","authors":"Li-Ping Wu, Yong-Xiang Wu, Xiang-Tao Ke, Pan Wang, Shuo Zhang, Yu-Ting Zhu, Ying Lu, Yu-Jie Shu, Shang-Yue Jiang, Chang-Jiang Li, Xiao-Qian Hu","doi":"10.1002/psc.3572","DOIUrl":"10.1002/psc.3572","url":null,"abstract":"<p>Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H<sub>2</sub>O<sub>2</sub>-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 μg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940135","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":"Small molecule– and peptide–drug conjugates addressing integrins: A story of targeted cancer treatment","authors":"Jannik Paulus, Norbert Sewald","doi":"10.1002/psc.3561","DOIUrl":"10.1002/psc.3561","url":null,"abstract":"<p>Targeted cancer treatment should avoid side effects and damage to healthy cells commonly encountered during traditional chemotherapy. By combining small molecule or peptidic ligands as homing devices with cytotoxic drugs connected by a cleavable or non-cleavable linker in peptide–drug conjugates (PDCs) or small molecule–drug conjugates (SMDCs), cancer cells and tumours can be selectively targeted. The development of highly affine, selective peptides and small molecules in recent years has allowed PDCs and SMDCs to increasingly compete with antibody-drug conjugates (ADCs). Integrins represent an excellent target for conjugates because they are overexpressed by most cancer cells and because of the broad knowledge about native binding partners as well as the multitude of small-molecule and peptidic ligands that have been developed over the last 30 years. In particular, integrin α<sub>V</sub>β<sub>3</sub> has been addressed using a variety of different PDCs and SMDCs over the last two decades, following various strategies. This review summarises and describes integrin-addressing PDCs and SMDCs while highlighting points of great interest.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3561","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931668","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}
Valeria Castelletto, Lucas de Mello, Emerson Rodrigo da Silva, Jani Seitsonen, Ian W. Hamley
{"title":"Comparison of the self-assembly and cytocompatibility of conjugates of Fmoc (9-fluorenylmethoxycarbonyl) with hydrophobic, aromatic, or charged amino acids","authors":"Valeria Castelletto, Lucas de Mello, Emerson Rodrigo da Silva, Jani Seitsonen, Ian W. Hamley","doi":"10.1002/psc.3571","DOIUrl":"10.1002/psc.3571","url":null,"abstract":"<p>The self-assembly in aqueous solution of three Fmoc-amino acids with hydrophobic (aliphatic or aromatic, alanine or phenylalanine) or hydrophilic cationic residues (arginine) is compared. The critical aggregation concentrations were obtained using intrinsic fluorescence or fluorescence probe measurements, and conformation was probed using circular dichroism spectroscopy. Self-assembled nanostructures were imaged using cryo-transmission electron microscopy and small-angle X-ray scattering (SAXS). Fmoc-Ala is found to form remarkable structures comprising extended fibril-like objects nucleating from spherical cores. In contrast, Fmoc-Arg self-assembles into plate-like crystals. Fmoc-Phe forms extended structures, in a mixture of straight and twisted fibrils coexisting with nanotapes. Spontaneous flow alignment of solutions of Fmoc-Phe assemblies is observed by SAXS. The cytocompatibility of the three Fmoc-amino acids was also compared via MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] mitochondrial activity assays. All three Fmoc-amino acids are cytocompatible with L929 fibroblasts at low concentration, and Fmoc-Arg shows cell viability up to comparatively high concentration (0.63 mM).</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3571","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905909","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}
Gia-Hoa Tran, Thi-Huyen Tran, Son H. Pham, Huy Luong Xuan, Tien T. Dang
{"title":"Cyclotides: The next generation in biopesticide development for eco-friendly agriculture","authors":"Gia-Hoa Tran, Thi-Huyen Tran, Son H. Pham, Huy Luong Xuan, Tien T. Dang","doi":"10.1002/psc.3570","DOIUrl":"10.1002/psc.3570","url":null,"abstract":"<p>Chemical pesticides remain the predominant method for pest management in numerous countries. Given the current landscape of agriculture, the development of biopesticides has become increasingly crucial. The strategy empowers farmers to efficiently manage pests and diseases, while prioritizing minimal adverse effects on the environment and human health, hence fostering sustainable management. In recent years, there has been a growing interest and optimism surrounding the utilization of peptide biopesticides for crop protection. These sustainable and environmentally friendly substances have been recognized as viable alternatives to synthetic pesticides due to their outstanding environmental compatibility and efficacy. Numerous studies have been conducted to synthesize and identify peptides that exhibit activity against significant plant pathogens. One of the peptide classes is cyclotides, which are cyclic cysteine-rich peptides renowned for their wide range of sequences and functions. In this review, we conducted a comprehensive analysis of cyclotides, focusing on their structural attributes, developmental history, significant biological functions in crop protection, techniques for identification and investigation, and the application of biotechnology to enhance cyclotide synthesis. The objective is to emphasize the considerable potential of cyclotides as the next generation of plant protection agents on the global scale.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692134","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}
Marco Bortolus, Aleksandra Kotynia, Giacomo Saielli, Paolo Ruzza, Marilena Di Valentin, Mauro Carraro, Justyna Brasuń
{"title":"Detailed investigation of the binding abilities of the heterodomain of a multiHis cyclopeptide toward Cu(II) ions","authors":"Marco Bortolus, Aleksandra Kotynia, Giacomo Saielli, Paolo Ruzza, Marilena Di Valentin, Mauro Carraro, Justyna Brasuń","doi":"10.1002/psc.3568","DOIUrl":"10.1002/psc.3568","url":null,"abstract":"<p>Cyclopeptides hold significant relevance in various fields of science and medicine, due to their unique structural properties and diverse biological activities. Cyclic peptides, characterized by intrinsically higher conformational order, exhibit remarkable stability and resistance to proteolytic degradation, making them attractive candidates for developing targeted drug delivery systems. The aim of this work is to elucidate the unique coordination properties of the multi-His cyclic peptide with c(HDHKHPHHKHHP) sequence (HDCP – heterodomain cyclopeptide). This peptide, indeed, is able to form homo- and hetero-dinuclear complexes in a wide pH range, being thus a good chelator for Cu(II) ions. Herein, we present the results of a combined study, involving potentiometric, spectroscopic (UV–Vis, CD, and EPR), and computational investigations, on its coordination properties. To better understand the interaction pattern with Cu(II) metal ions, two other peptides, each one bearing only one of the two binding domains of HDCP are also considered in this study: c(HDHKHPGGKGGP) = CP1, c(GKGGKPHHKHHP) = CP2, which share sequence fragments of HDCP and allow separate investigations of its coordination domains.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692135","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}
Periklis Karamanis, Jimmy Muldoon, Cormac D. Murphy, Marina Rubini
{"title":"Total synthesis of antifungal lipopeptide iturin A analogues and evaluation of their bioactivity against F. graminearum","authors":"Periklis Karamanis, Jimmy Muldoon, Cormac D. Murphy, Marina Rubini","doi":"10.1002/psc.3569","DOIUrl":"10.1002/psc.3569","url":null,"abstract":"<p>The pursuit of novel antifungal agents is imperative to tackle the threat of antifungal resistance, which poses major risks to both human health and to food security. Iturin A is a cyclic lipopeptide, produced by <i>Bacillus</i> sp., with pronounced antifungal properties against several pathogens. Its challenging synthesis, mainly due to the laborious synthesis of the β-amino fatty acid present in its structure, has hindered the study of its mode of action and the development of more potent analogues. In this work, a facile synthesis of bioactive iturin A analogues containing an alkylated cysteine residue is presented. Two analogues with opposite configurations of the alkylated cysteine residue were synthesized, to evaluate the role of the stereochemistry of the newly introduced amino acid on the bioactivity. Antifungal assays, conducted against <i>F. graminearum</i>, showed that the novel analogues are bioactive and can be used as a synthetic model for the design of new analogues and in structure–activity relationship studies. The assays also highlight the importance of the β-amino acid in the natural structure and the role of the stereochemistry of the amino fatty acid, as the analogue with the D configuration showed stronger antifungal properties than the one with the L configuration.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139664251","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":"All-hydrocarbon stapling enables improvement of antimicrobial activity and proteolytic stability of peptide Figainin 2","authors":"Jingwen Xue, Yinxue Fu, Huang Li, Ting Zhang, Wei Cong, Honggang Hu, Zhiyuan Lu, Fang Yan, Yulei Li","doi":"10.1002/psc.3566","DOIUrl":"10.1002/psc.3566","url":null,"abstract":"<p>Figainin 2 is a cationic, hydrophobic, α-helical host-defense peptide with 28 residues, which was isolated from the skin secretions of the Chaco tree frog. It shows potent inhibitory activity against both Gram-negative and Gram-positive pathogens and has garnered considerable interest in developing novel classes of natural antibacterial agents. However, as a linear peptide, conformational flexibility and poor proteolytic stability hindered its development as antibacterial agent. To alleviate its susceptibility to proteolytic degradation and improve its antibacterial activity, a series of hydrocarbon-stable analogs of Figainin 2 were synthesized and evaluated for their secondary structure, protease stability, antimicrobial, and hemolytic activities. Among them, F2-12 showed significant improvement in protease resistance and antimicrobial activity compared to that of the template peptide. This study provides a promising strategy for the development of antimicrobial drugs.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139563704","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":"Identification, chemical synthesis, and receptor binding of a reptilian gecko ghrelin","authors":"Hidekazu Katayama, Hiroyuki Kaiya","doi":"10.1002/psc.3567","DOIUrl":"10.1002/psc.3567","url":null,"abstract":"<p>Ghrelin is known to be a gastrointestinal peptide hormone in vertebrates. It has a unique posttransrational modification, octanoylation, at the Ser side chain of the third position. In this study, we identified the genes encoding ghrelin and its receptor from the Schlegel's Japanese gecko <i>Gekko japonicus</i>. The C-terminal residue of gecko ghrelin was His, although the chemical synthesis method for the <i>O</i>-octanoyl peptide with a C-terminal His residue has not yet been well-established. Acyl-ghrelin has been synthesized using a Ser derivative without side chain protecting group in the solid-phase peptide synthesis, although this synthetic strategy has not yet been well-established. Here we show the efficient synthetic method with minimal side reactions, and <i>G. japonicus</i> ghrelin could be obtained in good yield. This would be useful and applicable to the synthesis of ghrelin from other animal species. The gecko ghrelin receptor was expressed in HEK 293 cells, which was fully responsive to the synthetic gecko ghrelin. These results indicate that the ghrelin system similar to mammals also exists in a reptilian gecko, <i>G. japonicus</i>.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545031","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}