Journal of Peptide Science最新文献

{"title":"Proteomic Analysis Reveals Proteins, Siderophores, and Exopolysaccharides Involved in Cd(II) Stress Response of the Heavy Metal–Tolerant Delftia lacustris B11CM Strain","authors":"Jefferson Beltrán,&nbsp;Juan Sebastian Gualtero,&nbsp;Maryeimy Varón-López,&nbsp;Cesar Jaramillo-Paéz,&nbsp;Ximena Carolina Pulido","doi":"10.1002/psc.70060","DOIUrl":"10.1002/psc.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>Heavy metal (HM) pollution, such as cadmium, significantly impacts ecosystems and poses serious risks to human health. In soil, it reduces fertility and agricultural productivity. On the other hand, bacteria employ several tolerance mechanisms in response to HM exposure, including the production of siderophores, exopolysaccharides, proteins, and peptides. This study aimed to identify the possible molecular mechanisms involved in Cd(II) tolerance in the <i>Delftia lacustris</i> B11CM strain using nano LC/MS–MS proteomic analysis, siderophore and exopolysaccharide assays, protein and thiol quantification, and the comparison of protein profiles obtained by SDS-PAGE. The results demonstrated the presence of siderophores, an increase in the production of exopolysaccharides, and thiol-rich compounds. A total of 80 proteins were detected in the presence of cadmium, which are involved in catalytic activity, metalloproteins or proteins that bind to different molecules, and transporters. These proteins participate in metabolism and cellular processes, with most of them located in the plasma membrane. These molecules likely enable this bacterium to survive in cadmium-contaminated environments and are directly associated with tolerance mechanisms, highlighting the potential of this strain to be used as a bioinoculant with agronomic interest or for bioremediation.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 11","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191879","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":"The Significance of Oligomer C-Terminus Design in Solid-Phase Synthesis of Peptide Nucleic Acid Tetramers With the Incorporation of γ-S-Monomer Units Based on L-Glu","authors":"Anna A. Esenina,&nbsp;Ivan A. Prohorov,&nbsp;Viacheslav V. Severov,&nbsp;Igor P. Smirnov,&nbsp;Timofey A. Luzyanin,&nbsp;Yulia G. Kirillova","doi":"10.1002/psc.70061","DOIUrl":"https://doi.org/10.1002/psc.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Peptide nucleic acids (PNAs) containing γ-<i>S</i>-modified monomers show promise for antisense applications but face synthetic challenges due to their charged backbone. This study aimed to optimize the Boc solid-phase synthesis protocol for L-Glu-based γ-S-PNA oligomers. We systematically evaluated four tetramer designs incorporating glycine or β-alanine C-terminal linkers, monitoring resin loading (0.1–0.2 mmol/g), chain elongation (via a novel N = M × Q mass-corrected metric), and cleavage stability. While monomer sequence order in the C-terminal region showed no significant impact, spacer presence proved critical: β-alanine linkers enabled target oligomer isolation (≤ 10% yields), whereas linker-free tetramers degraded during acidic cleavage. These findings establish a foundation for synthesizing γ-S-PNAs while highlighting the need for further linker optimization to improve yields.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 11","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146445","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":"Metal Ion–Induced Cross-Linking in Mucin-Inspired Peptide Hydrogels","authors":"Annelie Puhlmann,&nbsp;Cihan Baydaroglu,&nbsp;Boris Schade,&nbsp;Michael Gradzielski,&nbsp;Beate Koksch","doi":"10.1002/psc.70059","DOIUrl":"10.1002/psc.70059","url":null,"abstract":"<p>Mucus is the biological hydrogel that lines the mucosal surfaces of mammals and acts as a protective barrier. Its main proteinaceous component is mucin, the high molecular weight, degree of glycosylation, and hardly uniquely defined nature of which hamper precise structures/property investigations based on biological samples. In contrast, chemically precisely defined peptide model systems inspired by such natural glycoproteins represent synthetically readily obtainable tools with excellent properties for both fundamental research and biomedical applications. Herein, we report the design and characterization of a library of histidine- and monosaccharide-containing coiled coil peptides that form hydrogels to different degrees in the presence of divalent metal ions Cu²⁺, Zn²⁺, Ca²⁺, and Fe²⁺. Using rheology, circular dichroism, and transmission electron microscopy, we determined the viscoelastic properties and global structures of these glycopeptide materials. This study reflects the interplay between glycan identity, histidine position, and divalent metal ion on the mechanical strength of these hydrogels.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 11","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130799","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":"Antimicrobial Peptide Moricin Inhibits Streptococcus pneumoniae Growth Through Membrane Disruption: Insights From In Silico and In Vitro Studies","authors":"Imran Ahmad,&nbsp;Shayan Mohd,&nbsp;Afsana Begum,&nbsp;Mohd Saif,&nbsp;Ranjana Singh","doi":"10.1002/psc.70055","DOIUrl":"https://doi.org/10.1002/psc.70055","url":null,"abstract":"<div>\u0000 \u0000 <p>The rise of multidrug-resistant <i>Streptococcus pneumoniae</i> poses a major public health threat, necessitating novel therapeutic targets. Pneumococcal Surface Adhesin A (PsaA), a conserved surface lipoprotein, plays a key role in manganese acquisition, colonization and virulence. Immunization with PsaA elicits protective immunity, while fragment-based drug design has identified inhibitors disrupting its function. PsaA emerges as a promising molecular target for innovative therapeutic strategies against pneumococcal diseases. Antimicrobial peptides (AMPs) are crucial components of the innate immune system, providing a potent defence mechanism against a broad spectrum of pathogens. Moricin, an AMP initially identified in <i>Bombyx mori</i>, exhibits robust antimicrobial activity against Gram-positive bacteria. This study explores the inhibitory effects of moricin on <i>S. pneumoniae</i>, a significant human pathogen responsible for severe infections such as pneumonia, meningitis and sepsis. In silico analyses, including molecular docking and molecular dynamics simulations, revealed a strong interaction between moricin and the PsaA. In vitro studies corroborated the computational findings, demonstrating a dose-dependent inhibition of <i>S. pneumoniae</i> growth. Moricin induced bacterial membrane disruption, evidenced by increased membrane permeability, release of intracellular contents and altered membrane potential, highlighting the bactericidal mode of action. Furthermore, time-kill kinetics revealed rapid bacterial eradication, underscoring moricin's efficacy. Additionally, toxicity assays on the macrophage BV2 cell line demonstrated that moricin caused no significant structural or organelle damage, emphasizing its biocompatibility and safety. The integration of in silico and in vitro approaches provides comprehensive mechanistic insights into moricin's antimicrobial action and establishes its potential as a safe and effective therapeutic agent against <i>S. pneumoniae</i>.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 11","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111018","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":"Peptide Tags for Site-Selective Nonenzymatic Covalent Modification of Proteins","authors":"Delphine Nørgaard Møller,&nbsp;Christian Kofoed,&nbsp;Mikkel Boas Thygesen,&nbsp;Knud J. Jensen","doi":"10.1002/psc.70058","DOIUrl":"https://doi.org/10.1002/psc.70058","url":null,"abstract":"<p>Bioconjugation chemistry is an important tool for studying proteins, developing pharmaceutical agents, and for many other applications. Conventional methods for protein functionalization rely on chemoselective reactions but often have poor regioselectivity. Peptide tags facilitating site-selective chemical covalent modification of proteins are of great value in the synthesis of protein conjugates. Ideally, a protein would only have to be minimally mutated prior to chemical modification to avoid interfering with native protein folding, trafficking, and function. This short review summarizes the advances in the developments and applications of peptide tags for covalent modifications that proceed without enzymatic assistance.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 11","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110782","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":"Plant Hormone Cytokinin as Aggregation Modulator of Gelsolin Amyloidosis","authors":"Dev Seneviratne,&nbsp;Naomi Stock,&nbsp;Tyra Lewis,&nbsp;R. J. Neil Emery,&nbsp;Sanela Martic","doi":"10.1002/psc.70057","DOIUrl":"https://doi.org/10.1002/psc.70057","url":null,"abstract":"<p>Amyloidosis, a self-assembly of proteins or peptides, is associated with numerous degenerative diseases, such as gelsolin amyloidosis, which remain without a cure. Gelsolin protein is an actin-binding protein, but when aggregated in a diseased state, it is a potential drug target. Specifically, gelsolin mutations, N184K and D187Y, have been linked to renal amyloidosis and systemic progressive deposition of amyloids, respectively. Understanding how such mutations mitigate gelsolin aggregation and how this process can be prevented through small molecule inhibitors is of interest. Herein, we explored the efficacies of plant-based naturally occurring cytokinin (CK) molecules as aggregation modulators in vitro. Using various biophysical methods, such as spectroscopy and microscopy, the aggregation of wild-type gelsolin peptide 184NNGDCFILDL193 and its mutants (N184K, D187Y) was investigated. The mutations significantly promoted aggregation, which is of biological significance. The CK <i>trans</i>-zeatin (tZ) was a more effective disaggregation promoter compared with kinetin (Kin). The experimentally determined IC₅₀ values were in the 9–20 μM range. The mode of inhibition was identified as direct non-covalent complexation between the CK and the peptides by using mass spectrometry and molecular docking studies. Data show that CKs are promising amyloid modulators, which can be easily translatable to other amyloid systems.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 10","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058053","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":"Discovery of a Thrombin-Targeting Anticoagulant Peptide From Whitmania pigra via a “Computation-Guided Experimentation” Strategy","authors":"Yu-Tong Hua,&nbsp;Rui-Juan Dong,&nbsp;Yin Li,&nbsp;Zhao-Yu-Qing Su,&nbsp;Quan-Cheng Xin,&nbsp;Meng Shen,&nbsp;Ya-Xiong Liu,&nbsp;Xiu-Huan Guo,&nbsp;Yan Lei,&nbsp;Yu-Ting Zhang,&nbsp;Gai-Mei She,&nbsp;Peng Wei,&nbsp;Rui-Juan Yuan","doi":"10.1002/psc.70056","DOIUrl":"https://doi.org/10.1002/psc.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Targeting thrombin to screen safe thrombin inhibitors from natural plants and animals is a critical direction in anticoagulant drug development. This study aimed to screen thrombin inhibitors from the nonbloodsucking leech <i>Whitmania pigra</i> (WP) and elucidate the mechanism of anticoagulation through a “computation-guided experimentation” strategy. A peptide library was constructed from WP hydrolysates, and virtual screening was performed using molecular docking and dynamics simulations. A novel thrombin-targeting anticoagulant peptide PEP^WP (LRELEDALEQER) was screened out from the peptide library and validated through in vitro/in vivo experiments. PEP^WP significantly prolonged thrombin time (TT) and prothrombin time (PT) in a dose-dependent manner in vitro, indicating its role in the common and extrinsic coagulation pathways. Surface plasmon resonance (SPR) analysis then confirmed strong thrombin binding (<i>K</i>_<i>d</i> = 7.242 × 10⁻⁶ mol/L). Furthermore, PEP^WP prolonged TT while reducing blood viscosity in acute blood stasis rats. Finally, structural analysis revealed that PEP^WP bound to Exosite II of thrombin. Arg233 and Arg101 were the key residues for the binding. In conclusion, PEP^WP exhibited good anticoagulant activity and significant application potential.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 10","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011931","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":"Amphipathic Octenyl-Alanine Modified Peptides Mediate Effective siRNA Delivery","authors":"Tõnis Lehto,&nbsp;Marit Isakannu,&nbsp;Helena Sork,&nbsp;Annely Lorents,&nbsp;Safa Bazaz,&nbsp;Oscar P. B. Wiklander,&nbsp;Samir EL Andaloussi,&nbsp;Taavi Lehto","doi":"10.1002/psc.70054","DOIUrl":"https://doi.org/10.1002/psc.70054","url":null,"abstract":"<p>The development of therapeutic small interfering RNAs (siRNAs) has lately gained significant momentum due to their ability to silence genes in a highly specific manner. The main obstacle withholding the wider translation of siRNA-based drug modalities is their limited half-life and poor bioavailability, especially in extra-hepatic tissues. Consequently, various drug delivery systems (DDSs) have been developed to improve the delivery of siRNAs, including short delivery peptides called cell-penetrating peptides (CPPs). In this study, we explore the potential of using alkenyl-alanine modifications to enhance the siRNA delivery efficacy with CPPs. We demonstrate on hPep peptides that incorporation of alkenyl-alanines enhances the encapsulation of siRNAs into stable nanoparticles and contributes to increased cellular uptake. Furthermore, we demonstrate that the lead peptide, hPep3, induces effective RNAi-mediated gene silencing in a reporter cell model as well as on the disease-implicated endogenous CD45 gene target. The biodistribution studies in mice show that the alkenyl-alanines are systemically well tolerated, and employing such modifications in the peptide backbone improves siRNA delivery in several tissues, including extra-hepatic sites. As demonstrated on hPep peptides, alkenyl-alanines offer a simple yet robust way to enhance the delivery efficacy of CPPs and have the potential to advance siRNA therapeutics beyond the liver targets.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 10","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012177","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":"Leveraging the Therapeutic Potential of Natural Peptide Panurgines: Hydrocarbon Stapling Strategy Enhances Their Efficacy Against Breast Cancer","authors":"Zhongzhong Peng,&nbsp;Lei Chen,&nbsp;Xianyuan Miao,&nbsp;Qiongqiong Wang,&nbsp;Shuyue Fu,&nbsp;Xikai Zhang,&nbsp;Xiao Zhou,&nbsp;Sijia Ren,&nbsp;Yehua Lao,&nbsp;Yinghua Li,&nbsp;Kaifeng Wang,&nbsp;Shipeng He","doi":"10.1002/psc.70047","DOIUrl":"https://doi.org/10.1002/psc.70047","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of novel candidate molecules for breast cancer treatment holds significant clinical value. Panurgines (<b>PNG</b>), derived from the venom of the wild bee <i>Panurgus calcaratus</i>, are particularly noteworthy for their anti-breast cancer activity and antibacterial properties. However, linear peptides are often hindered by poor stability and limited cell membrane permeability, making them highly susceptible to protease degradation. To tackle this challenge, the current study focused on synthesizing a range of stapled Panurgines peptides through hydrocarbon stapling modifications, followed by a comprehensive evaluation of their chemical and biological properties. Remarkably, <b>PNG-5</b> demonstrated notable improvements in helicity, cell membrane permeability, proteolytic stability, and antitumor activity. This study examines how the hydrocarbon stapling technique significantly affects the secondary structure, hydrolase stability, and biological activity of <b>PNG</b>, revealing its potential as a transformative and powerful anti-breast cancer therapeutic. These findings lay a strong foundation for the development of innovative and highly effective peptide-based anti-tumor drugs.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 10","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923833","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":"DiPTH-Cystine and PTH-Cysteine in Disulfide Bond Analysis Using Automated Edman Degradation","authors":"Toni Kühl,&nbsp;Yomnah Y. Elsayed,&nbsp;Alexander Terekhov,&nbsp;Diana Imhof","doi":"10.1002/psc.70053","DOIUrl":"https://doi.org/10.1002/psc.70053","url":null,"abstract":"<p>The annotation of disulfide bridges in peptides and proteins can be an elaborate process and requires careful revision of multiple data sets to avoid wrong assignment in the structural analysis. Herein, we provide additional support to elucidate the cysteine connectivity by re-implementation of Edman sequencing for the analysis of this specific structural feature. By synthesizing diPTH-cystine and PTH-cysteine for comparison, we were able to identify the respective derivative during Edman sequencing when a disulfide bond is detected in a peptide. Application of Edman sequencing to selected peptides with two or three disulfide bridges provides further insight into the differentiation of cysteines that form a disulfide bridge for both half-cystines in the same cycle and in separated cycles. A combined approach for the implementation of automated Edman sequencing in the process of disulfide bond assignment is described to alleviate structural elucidation in the future analysis of cysteine-rich peptides and proteins.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 10","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915213","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}