Journal of Peptide Science最新文献

{"title":"Chemical Synthesis and Biological Evaluation of the Insecticidal Peptide AaIT5 Identified From the Androctonus australis Venom","authors":"Shoichi Sakai,&nbsp;Yoshiaki Nakagawa,&nbsp;Masahiro Miyashita","doi":"10.1002/psc.70125","DOIUrl":"10.1002/psc.70125","url":null,"abstract":"<div>\u0000 \u0000 <p>Scorpion venom contains various bioactive peptides. Voltage-gated sodium channel toxins (NaTxs) have been the primary focus of scorpion venom research because of their significant potency and high selectivity. A variety of NaTxs have been identified in the venom of <i>Androctonus australis</i>, six of which exhibit insecticidal activity. Among these, the biological activity of AaIT5 remains poorly characterized because of its low abundance in the venom. In this study, AaIT5 was chemically synthesized via native chemical ligation (NCL), suppressing side reactions associated with aspartimide formation using specialized Fmoc-protected amino acids, followed by oxidative folding. Subsequent LC/MS/(MS) analyses of the enzymatic digests confirmed that the synthetic peptide adopted the disulfide bond pattern predicted from the related NaTxs. Synthetic AaIT5 exhibited insecticidal activity against both <i>Spodoptera litura</i> and <i>Acheta domesticus</i>, although it was less potent than related insecticidal NaTxs such as LqhIT2. Sequence alignment and molecular modeling suggested that the reduced activity results from the substitution of a highly conserved tryptophan residue with valine, thereby abolishing a potential cation–π interaction with insect sodium channels. The successful chemical synthesis and functional characterization of AaIT5 provide a robust platform for the preparation of toxin analogs and further studies on the structure–activity relationships of insecticidal NaTxs.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808762","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":"Synergistic Antibacterial and Antibiofilm Effects of (KW)4 in Combination With Antibiotics Against Listeria monocytogenes","authors":"Jonggwan Park,&nbsp;Da Dam Kang,&nbsp;Yujin Lim,&nbsp;Jun Hee Oh,&nbsp;Hyeongsun Kim,&nbsp;Chanhyeok Moon,&nbsp;Jinyoung Lee,&nbsp;Seokjin Choi,&nbsp;Yoonkyung Park","doi":"10.1002/psc.70126","DOIUrl":"10.1002/psc.70126","url":null,"abstract":"<div>\u0000 \u0000 <p>The efficacy of antibiotics is increasingly limited by microbial resistance, necessitating the development of alternative therapeutic strategies. The combination of conventional antibiotics with antimicrobial peptides (AMPs) has emerged as a promising approach for enhancing antibacterial activity. <i>Listeria monocytogenes</i> is an important foodborne pathogen that causes listeriosis—a severe invasive infection associated with high morbidity and mortality, particularly in pregnant women, neonates, older adults, and immunocompromised individuals. (KW)₄ is a peptide composed of four repeats of lysine (Lys) and tryptophan (Trp), exhibiting both cationic and hydrophobic characteristics. Because of these structural properties, (KW)₄ reportedly exhibits antimicrobial activities. However, its combined effects with conventional antibiotics have not yet been investigated. Here, we evaluated the synergistic effects of (KW)₄ in combination with cefotaxime or tetracycline against <i>L. monocytogenes</i>. These combinations displayed synergistic antimicrobial activity, as determined by the fractional inhibitory concentration index, and were more effective at lower concentrations than the individual agents. The combination exerted sustained bactericidal effects for up to 12 h and inhibited biofilm formation. No significant hemolytic activity or cytotoxicity was observed in RAW264.7 cells under the tested conditions. These results suggested that (KW)₄ has potential as an antibiotic adjuvant against <i>L. monocytogenes</i>.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813406","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":"Serendipitous Discovery of Short Peptides Dimethylammonium Salt Promoting Neural Differentiation","authors":"Sadiq Noor Khan,&nbsp;Maha Shahid,&nbsp;Shahzad Nazir,&nbsp;Anila Bashir,&nbsp;Sumbla Sheikh,&nbsp;Shabana Usman Simjee,&nbsp;Marc Maresca,&nbsp;Farzana Shaheen","doi":"10.1002/psc.70124","DOIUrl":"https://doi.org/10.1002/psc.70124","url":null,"abstract":"<p>The synthesis and in vitro neuronal growth support activity of a novel series of heptapeptides (<b>1</b>–<b>19</b>) are reported here. Structural studies of the peptide <b>3</b> (LSAVTFG.DMA) revealed an unexpected dimethylammonium (DMA) salt adduct formation localized at the <i>C</i>-terminal glycine residue. DOSY NMR analysis revealed the presence of two distinct species exhibiting different diffusion coefficients, allowing the differentiation between the peptide and the DMA adduct. Peptide <b>3</b> promoted neural differentiation at 100 μM concentration. To identify residues crucial for biological activity, we conducted L- and D-alanine scans with salt and nonsalt form of peptide <b>3,</b> which resulted in the synthesis of 16 peptide analogs. Findings from the alanine scan revealed that the lead peptides L1A.DMA (<b>13</b>) and S2A.DMA (<b>15</b>) exhibited significant neural progenitor cells or neural stem cells (NPCs/NSCs) differentiation activity. These peptides promote neuronal survival, morphology recovery, increase cell proliferation, and preserve neuronal network integrity under OGD/R and hypoxia/R insult in an in vitro model of ischemic stroke. These results represent the first synthetic approach to new neuromodulatory peptides and deliver important structure–activity relationship (SAR) insights to guide the development of bioactive peptides.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784992","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":"Erratum to “Edge-Grafted Polyarginine Functionalization of Graphene Nanocarriers Maintains Noncovalent Aromatic Drug Loading”","authors":"","doi":"10.1002/psc.70123","DOIUrl":"10.1002/psc.70123","url":null,"abstract":"<p>\u0000 <span>B. Scagnoli</span>, <span>A. Semeraro</span>, <span>K. Hu</span>, et al., <i>Journal of Peptide Science</i> <span>32</span>, no. <span>8</span> (<span>2026</span>): e70114, https://doi.org/10.1002/psc.70114.\u0000 </p><p>In the published version of this article, the images for Chart 1 and Scheme 1 were inadvertently interchanged. The captions for Chart 1 and Scheme 1 remained in their correct positions as published.</p><p>We apologize for this error.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765158","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":"Celebrating Young Investigators in Peptide Science","authors":"William D. Lubell,&nbsp;John D. Wade,&nbsp;Paolo Rovero","doi":"10.1002/psc.70120","DOIUrl":"10.1002/psc.70120","url":null,"abstract":"","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673896","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":"No Significant Secondary Structural Change of α-Synuclein Monomer by Site-Specific DOPA or Phosphorylation Introduction in Its C-Terminal Region","authors":"Tatsuhito Matsuo,&nbsp;Isao Suetake,&nbsp;Mariko Kimura,&nbsp;Satoshi Hashimoto,&nbsp;Koichi Matsuo,&nbsp;Sakiko Matsumoto,&nbsp;Shinji Hirotsune,&nbsp;Hironobu Hojo","doi":"10.1002/psc.70118","DOIUrl":"10.1002/psc.70118","url":null,"abstract":"<p>α-Synuclein (αSyn) is a major component of pathogenic Lewy bodies and Lewy neurites and is closely associated with Parkinson's disease. Among the various posttranslational modifications of αSyn, several have been implicated in the degeneration of dopaminergic neurons and are thought to promote Parkinson's disease through enhanced misfolding, aggregation, and accumulation of αSyn. Two such modifications, phosphorylation at Ser¹²⁹ (S129Phos) and hydroxylation at Tyr¹³⁶ (Y136DOPA), exert distinct effects on αSyn aggregation: S129Phos has been reported to either inhibit or promote aggregation, whereas Y136DOPA induces the formation of short oligomeric species. To gain insight into the molecular basis underlying the initiation of αSyn multimerization, we semisynthesized αSyn carrying either S129Phos or Y136DOPA and prepared recombinant unmodified full-length αSyn as a control. Vacuum-ultraviolet circular dichroism (VUVCD) spectroscopy revealed that these αSyn variants in their monomeric states possessed essentially identical secondary structures. These results suggest that the modifications themselves do not induce significant secondary structural changes in monomeric αSyn.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679064","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":"Peptide Therapeutics for Solid Tumors: Functional Classes, AI-Enhanced Discovery and Clinical Advances","authors":"Jinqiu Liang,&nbsp;Xiaochuan Tang,&nbsp;Haoqi Li,&nbsp;Yan Fang,&nbsp;Feng Jiang","doi":"10.1002/psc.70119","DOIUrl":"10.1002/psc.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>Solid tumors, the most prevalent form of malignancy, pose therapeutic challenges distinct from hematologic malignancies due to their complex biology, including high tumor heterogeneity, a dense extracellular matrix (ECM), an immunosuppressive tumor microenvironment (TME), and multifaceted drug resistance. Peptide drugs have emerged as a focal point in precision oncology, combining the deep tissue penetration of small molecules with the high target specificity, low immunogenicity, and sequence designability of antibodies. This review systematically summarizes advancements in peptide-based therapeutics for solid tumors from 2020 to 2025. These agents are categorized by function into five classes: tumor-homing peptides, surface receptor antagonist/inhibitory peptides, interfering peptides, peptide vaccines, and cell-penetrating peptides as delivery tools. We also highlight the transformative role of artificial intelligence (AI) in peptide design and discovery. Finally, we discuss outcomes from clinical trials of peptide drugs in solid tumors, underscoring their potential as multifunctional agents in this setting.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673940","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":"Gold Nanoparticles Coated With the Antimicrobial Peptide Os-C(W5): Anticandidal and Biological Activity","authors":"P. J. Palm,&nbsp;R. R. Chirombo,&nbsp;C. K. Chiramba,&nbsp;J. C. Serem,&nbsp;H. Taute,&nbsp;M. van der Walt,&nbsp;A. R. M. Gaspar,&nbsp;M. J. Bester","doi":"10.1002/psc.70117","DOIUrl":"https://doi.org/10.1002/psc.70117","url":null,"abstract":"<p><i>Candida albicans</i> is a critical-priority fungal pathogen due to its global burden of infection, biofilm-forming ability, and increasing drug resistance. Previously, the tick-derived antimicrobial peptide (AMP), Os-C, demonstrated antifungal, antioxidant, and nitric oxide (NO) scavenging activity. Subsequent tryptophan end-tagging produced Os-C(W₅) which improved antifungal activity and reduced salt sensitivity; however, the proteolytic susceptibility of Os-C(W₅) remained a limitation.</p><p>Researchers have shown that N-terminal tryptophan tagging of a gold binding peptide generated gold nanoparticle (GNPs) of a clinically relevant size. We successfully applied this method with minor modifications to generate GNPs coated with Os-C(W₅). GNP@Os-C(W₅) exhibited an average diameter of 14.2 ± 0.32 nm, with preserved peptide disorder in peptide secondary structure after conjugation. Compared with free Os-C(W₅), GNP@Os-C(W₅) activity against planktonic <i>C. albicans</i> was reduced, but antibiofilm activity was maintained, associated with a reduction in biofilm biomass. Ultrastructural changes to planktonic <i>C. albicans</i> included roughened and irregular surfaces, membrane indentations, and extracellular debris indicating cell lysis. Samples treated with Os-C(W5) and GNP@Os-C(W5) showed visibly less dense biofilm architecture and fewer apparent hyphal structures relative to the untreated control. Both Os-C(W₅) and GNP@Os-C(W₅) were non-cytotoxic to HaCat cells. Most importantly, resistance to the protease trypsin was increased. However, antioxidant properties of Os-C(W₅) were lost with GNP conjugation, whereas both Os-C(W₅) and GNP@Os-C(W₅) compared with Os-C lacked NO scavenging activity. Overall, this method of GNP conjugation provides a viable strategy to achieve enhanced AMP stability, retained antifungal activity, although the ability of GNP@Os-C(W₅) to reduce oxidative stress was compromised.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652442","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":"Peptide Conformational Determination With Vibrational Circular Dichroism and Isotope Labeling: Focused Review of 310-Helical Peptide Spectroscopic Structural Studies","authors":"Timothy A. Keiderling","doi":"10.1002/psc.70116","DOIUrl":"10.1002/psc.70116","url":null,"abstract":"<div>\u0000 \u0000 <p>Optical spectroscopic techniques have long been used to determine average secondary structure in proteins and peptides, but these are primarily limited to determination of relative sheet and helix content, with the remainder often designated as “other.” Several decades ago, in cooperation with Claudio Toniolo and co-workers, our group at UIC was able to show that vibrational circular dichroism (VCD) could be used to distinguish between formation of 3₁₀-helices and α-helices in small peptides, as well as from other uniform structures. Conventional electronic CD (ECD) or infrared (IR) spectroscopy did not give unambiguous distinctions between these two right-handed, internally H-bonded, helical forms. Theoretical modeling of the VCD spectra showed that the differences between helical forms could not be attributed to just use of Aib residues or of organic solvents, both used to stabilize the 3₁₀ conformation. Later we showed that, with IR and VCD enhanced by isotopic labeling, it was possible to differentiate site-specific structures using vibrational spectra interpreted with DFT-level theoretical modeling. These advances are briefly reviewed here and results of applying them to 3₁₀-helical structures are discussed.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422089","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":"Edge-Grafted Polyarginine Functionalization of Graphene Nanocarriers Maintains Noncovalent Aromatic Drug Loading","authors":"Beatrice Scagnoli,&nbsp;Alessandro Semeraro,&nbsp;Kaiyue Hu,&nbsp;Alberto Ongaro,&nbsp;Agnese Pavan,&nbsp;Luigi Brambilla,&nbsp;Chiara Castiglioni,&nbsp;Maria Cristina De Rosa,&nbsp;Giuseppe Pappalardo,&nbsp;Giuseppina Sabatino,&nbsp;Michele Maggini","doi":"10.1002/psc.70114","DOIUrl":"10.1002/psc.70114","url":null,"abstract":"<p>Covalent peptide grafting is widely used to improve the biological performance of nanocarriers, especially through cell-penetrating peptides (CPPs) that enhance cellular uptake. However, when drug loading relies on noncovalent interactions, peptide functionalization may interfere with surface adsorption processes. This concern is particularly relevant for graphene-based nanocarriers, where π-conjugated molecules bind via π–π interactions on the basal plane. Here, we present an orthogonal functionalization strategy in which peptide conjugation occurs selectively at the edges of graphene nanoparticles (B60), which bear carboxylic acid groups, while π-conjugated cargo is adsorbed on the basal plane. Poly-arginine-11 (R11) was covalently immobilized, preserving the aromatic surface for π-π interactions. Using 1-pyrenecarboxylic acid and compound <b>8</b>, a π-conjugated NEK6 inhibitor, we show that R11 grafting does not affect loading capacity or thermally induced release. Spectroscopic and microscopic analyses confirm that the basal plane remains intact and accessible after functionalization. Molecular dynamics simulations indicate that peptide chains form a flexible, charged corona at the nanoparticle periphery without perturbing molecule–graphene interactions. Overall, edge-grafted R11 preserves π-π-mediated loading and supports the design of peptide–graphene hybrid systems for delivering poorly soluble aromatic bioactive compounds.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"32 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391247","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}