Biomolecules最新文献

{"title":"HSP90 Inhibitor, AT13387 Mitigates Chronic Lung Injury in Pre-Pubertal Mice: A Therapeutic Axis in Bronchopulmonary Dysplasia.","authors":"Pavel A Solopov, Christiana Dimitropoulou, John D Catravas, Ruben M L Colunga Biancatelli","doi":"10.3390/biom16091320","DOIUrl":"10.3390/biom16091320","url":null,"abstract":"<p><p>Exposure to hydrochloric acid (HCl) can provoke severe chronic pulmonary injury. Children are particularly vulnerable due to their smaller airways, higher respiratory rate, and stronger inflammatory response; yet no countermeasures exist for HCl-induced chronic lung injury in the pediatric population. We have previously demonstrated the involvement of HSP90 during HCl-induced lung injury in pre-pubertal (p24) mice, who develop stronger persistent inflammation with higher NLRP3 inflammasome activation, but less pulmonary fibrosis compared to adults. Here, we tested the hypothesis that post-treatment with the second-generation HSP90 inhibitor AT13387 (Onalespib), administered subcutaneously beginning 24 h after HCl instillation, would prevent HCl-induced chronic lung injury and pulmonary fibrosis in young (p24) C57BL/6J mice. Pre-pubertal (p24) C57BL/6J mice received a single intratracheal instillation of 0.1 N HCl and were treated with AT13387 (10 mg/kg, s.c., 3×/week for 30 days) beginning 24 h post-exposure. Bronchoalveolar lavage fluid (BALF) analysis, lung function measurements, histological assessment (Ashcroft fibrosis score), and Western blot analysis of key signaling mediators were performed. Additionally, publicly available single-nucleus RNA sequencing (snRNA-Seq) data from a cohort of 13 infants with bronchopulmonary dysplasia (BPD) and 11 age-matched controls were analyzed to evaluate HSP90 isoform expression in human pediatric lung disease. AT13387 significantly reduced BALF white blood cell concentration without affecting total BALF protein levels. Importantly, AT13387 did not impair normal weight gain or development over the 30-day observation period. AT13387 abrogated HCl-induced expression of TGF-β1, phosphorylation of HSP90, ERK1/2, SMAD2, IκBα, and upregulation of the inflammasome NLRP3. Additionally, AT13387 prevented changes in lung function dynamics and reduced the Ashcroft fibrosis score. Analysis of the human snRNA-Seq BPD dataset revealed a widespread pan-overexpression of all three HSP90 isoforms, i.e., HSP90AA1, HSP90AB1, and HSP90B1. These findings suggest that the HSP90 inhibitor AT13387 exhibits strong antidotal properties against HCl-induced chronic lung injury and pulmonary fibrosis in a pre-clinical pediatric model and identify HSP90 as a conserved therapeutic target in pediatric chronic lung disease.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Nuclear SUMO-Targeted Ubiquitin Ligase Uls2 (Slx5-Slx8) in Quality Control of Cytosolic Proteins.","authors":"Friederike Profe-Austermann, Lennard-Maximilian Döring, Luisa Schmidt, Lena Avci, Maximilian Haka, Ganapathi Kandasamy, Judith Müller, Nils Johnsson, Marcus Krüger, R Jürgen Dohmen","doi":"10.3390/biom16091322","DOIUrl":"10.3390/biom16091322","url":null,"abstract":"<p><p>The interplay between the posttranslational modifiers SUMO and ubiquitin mediates the degradation of proteins. This crosstalk is conveyed by SUMO-targeted ubiquitin ligases (STUbLs). The best-studied STUbL in <i>Saccharomyces cerevisiae</i> is the heterodimer Slx5-Slx8 (Uls2). Uls2 mainly resides in the nucleus and is involved in stress tolerance, DNA repair and genome stability maintenance. So far, the majority of known Uls2 targets are nuclear proteins. The role of Uls2 in the targeting of cytosolic proteins remains to be elucidated. In this study, we identify Nis1 and Fir1 as two cytosolic proteins that become substrates of Uls2 in the absence of their partner polypeptides, which results in their SUMO-dependent aggregate formation in the nucleus. To uncover further Uls2 targets, we performed whole-cell proteomics of <i>slx5Δ</i> cells with and without oxidative stress. Comparison to wild-type cells revealed a large pool of potential Uls2 substrates, a subset of which is targeted upon oxidative stress, suggesting a quality control (QC) mechanism. Based on our results, we propose a role for Uls2 in a QC system targeting cytosolic proteins lacking their partners or that are damaged, for example, by oxidation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-Specific Chemerin in Atherosclerosis.","authors":"Muyun Chen, Yuxin Li, Linling Feng, Longhua Liu","doi":"10.3390/biom16091327","DOIUrl":"10.3390/biom16091327","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disability-adjusted life years (DALYs) and all-cause mortality worldwide, imposing an increasing global health burden. Atherosclerosis (AS) is a complex multifactorial disease, and the concept of organ crosstalk has provided a new perspective for understanding its pathogenesis. Although circulating chemerin levels are closely associated with the development and adverse prognosis of ASCVD, the functional heterogeneity and regulatory characteristics of chemerin derived from different tissues have not been systematically investigated. This review elucidates the tissue-specific roles of chemerin in AS from both endocrine and paracrine perspectives, with a focus on chemerin derived from the liver, white adipose tissue, perivascular adipose tissue, and epicardial adipose tissue. Endocrine chemerin primarily contributes to systemic metabolic dysfunction and endothelial injury, whereas locally produced chemerin regulates vascular smooth muscle cell remodeling and vascular inflammation through paracrine signaling. Collectively, endocrine and paracrine chemerin constitute a dual regulatory network that links metabolic abnormalities with vascular remodeling during AS progression.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on Bidirectional Regulation of the Microbiota-Gut-Brain Axis in Autism Spectrum Disorder Based on the Immune-Metabolic-Endocrine Interactive Network.","authors":"Weiao Kong, Haoke Qiu, Yuhang Jiang, Huanhuan Ge, Wanyi Wu, Lefan Huang, Lisheng Chu, Lijun Ge","doi":"10.3390/biom16091321","DOIUrl":"10.3390/biom16091321","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by core features of social communication deficits and high prevalence of gastrointestinal comorbidities. With its continuously rising global prevalence, current therapeutic modalities remain unable to target and ameliorate the core symptoms of ASD. The microbiota-gut-brain axis (MGBA), a critical pathway mediating crosstalk between the gut microbiota and the brain, has been extensively documented to be deeply involved in the pathological progression of ASD in recent years. However, prior studies have predominantly focused on the unidirectional regulation of the brain by gut microbiota, lacking an integrated account of the bidirectional regulation across immune, metabolic, and endocrine systems. Centered on the immune-metabolic-endocrine interactive network, this review systematically delineates the bidirectional regulatory mechanisms of the MGBA in ASD by integrating recent evidence from microbiota sequencing, animal models, and clinical intervention studies, with the aim of clarifying the bidirectional causal controversy between intestinal microecological disturbance and ASD behavioral abnormalities. This review proposes that in children with ASD, decreased abundance of beneficial intestinal bacteria and disrupted metabolic profiles of short-chain fatty acids synergistically impair intestinal barrier integrity, triggering peripheral chronic inflammation that further drives excessive microglial activation-mediated central neuroinflammation. Subsequently, disturbances in the homeostasis of multiple neurotransmitters including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), histamine, and dopamine occur via the vagus nerve and hypothalamic-pituitary-adrenal (HPA) axis, ultimately driving ASD behavioral abnormalities. Conversely, chronic stress and behavioral characteristics associated with ASD reshape the intestinal microecology through neuroendocrine pathways, forming a vicious cycle of \"microbiota dysbiosis-immune inflammation-HPA axis hyperactivity-further intestinal microecological imbalance\". This review summarizes the therapeutic efficacy and translational bottlenecks of three types of microecological interventions: fecal microbiota transplantation (FMT), probiotics, and ketogenic diet, and analyzes the current limitations in the field, including pronounced population heterogeneity, unclear cross-talk mechanisms among multiple pathways, and the scarcity of large-sample clinical evidence. Collectively, this review preliminarily elucidates the complete multi-system interactive framework of MGBA regulation in ASD, providing theoretical support for mechanistic research and gut-targeted individualized interventions for ASD.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Lomefloxacin-Triazole Hybrids: Design, Synthesis and In Vitro Antiproliferative Activity in Breast, Melanoma and Colon Cancer Cell Lines.","authors":"Justyna Nowakowska, Zuzanna Rzepka, Andrzej Bak, Dorota Wrześniok, Krzysztof Marciniec","doi":"10.3390/biom16091323","DOIUrl":"10.3390/biom16091323","url":null,"abstract":"<p><p>In recent years, extensive research has focused on fluoroquinolone-triazole hybrids, with particular emphasis on structural modifications of ciprofloxacin. In the present study, novel derivatives of lomefloxacin with a 1,4-disubstituted-1,2,3-triazole moiety were designed, synthesised, and biologically evaluated at the N4 position of the piperazine ring. Molecular docking studies suggested potential interactions of the designed compounds with topoisomerase I, with docking scores comparable to that of the reference compound camptothecin. Molecular dynamics simulation suggested short-term conformational stability of the ligand-based (holo) topoisomerase IIβ modulator. The synthesis was accomplished using a copper(I)-catalysed azide-alkyne cycloaddition, leading to the formation of nine new compounds. A preliminary evaluation of antiproliferative activity was performed on selected human cancer cell lines using the WST-1 assay, while selectivity against normal human dermal fibroblast was assessed. The results obtained revealed promising antiproliferative activity of the tested derivatives, particularly against colorectal cancer cell lines.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane Disruption and Charge Neutralization Drive Synergy Between LL37-Derived Peptides and Polymyxins Against <i>E. coli</i>.","authors":"Wenxu Han, Nicholas James Watkins, Terri Anne Camesano","doi":"10.3390/biom16091324","DOIUrl":"10.3390/biom16091324","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Antimicrobial peptides (AMPs) offer promising strategies for combating drug-resistant bacteria such as <i>Escherichia coli</i> (<i>E. coli</i>). This study evaluated the synergistic effects of the human-derived AMP LL37 and its fragments FK16 and FK13, in combination with polymyxin B, colistin, and vancomycin, against three <i>E. coli</i> strains in vitro. <b>Methods</b>: Because the outer membrane of <i>E. coli</i> acts as a barrier to antimicrobial agents, we assessed the membrane-permeabilizing activity of these AMPs. We further examined electrostatic interactions between the cationic AMPs and bacterial surfaces via zeta potential measurements. To simulate physiological conditions, we investigated how Mg²⁺ and Ca²⁺ ions, common in blood, stabilize the bacterial outer membrane and influence AMP activity. Additionally, we assessed cytoplasmic membrane permeabilization as a key mechanism of antibacterial action. Finally, to support clinical translation, we evaluated the cytotoxicity of the AMPs on human dermal fibroblasts. <b>Results</b>: Checkerboard assays revealed that the peptide-antibiotic combinations exerted synergistic effects against the tested <i>E. coli</i> strains in both MHB medium and cation-adjusted MHB medium, with FICI values ranging from 0.3125 to 0.5 and <0.375 to 0.5, respectively. All three AMPs (LL37, FK16, and FK13) exhibited strong outer membrane-permeabilizing activity. Zeta potential measurements revealed a correlation between membrane disruption and surface charge neutralization. The presence of Mg²⁺ and Ca²⁺ ions was found to stabilize the bacterial outer membrane. Cytoplasmic membrane permeabilization was confirmed as a key antibacterial mechanism. Cytotoxicity assays confirmed the safety profile of these AMPs on human cells. <b>Conclusions</b>: The study demonstrates that LL37 and its fragments enhance the activity of conventional antibiotics against <i>E. coli</i> through membrane disruption and charge neutralization, as evidenced by the FICI values (0.3125-0.5), membrane disruption and charge neutralization. While divalent cations in physiological conditions influence AMP efficacy, these peptides show potential for clinical application against <i>E.coli</i>.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCL10 Is Inhibited by PPARβ/δ-Selective Activation in Human Monocyte-Derived Dendritic Cells, T Lymphocytes and Monocytes In Vitro: Insights into Autoimmune Rheumatic Diseases.","authors":"Gabriele Farina, Mariangela Sottili, Giada La Spina, Stefania Gelmini, Simona Truglia, Fabrizio Conti, Francesca Romana Spinelli, Clara Crescioli","doi":"10.3390/biom16091325","DOIUrl":"10.3390/biom16091325","url":null,"abstract":"<p><p>The chemokine CXCL10 contributes to early autoimmune rheumatic disease (ARD) development. Preclinical ARD stages exhibit dendritic cells (DCs), CD4⁺ T cells, and monocytes (CD14⁺ cells) dysregulation and an overreactive immunoprofile. The peroxisome proliferator-activated receptor (PPAR)β/δ acts as a \"molecular brake\", limiting autoimmune overresponse. This study aims to investigate CXCL10 in human monocyte-derived mDCs, CD4⁺ T cells, and monocytes exposed to PPARβ/δ agonist carbaprostacylin (cPGI₂) or PPARγ agonist rosiglitazone (RGZ), to verify drug-class-related effects. Tumor necrosis factor (TNF)α, interferon (IFN)γ, synergistic inducers of CXCL10, and interleukin (IL)-10 were investigated. mDCs, CD4⁺ T cells, and CD14⁺ monocytes isolated from healthy donors' blood were cultured, specifically activated to mimic an overreactive phenotype, and treated for 24-48 h with/without [10 μM] cPGI₂ or [5 μM] RGZ (near therapy doses, respectively). Luminex assays quantified cell supernatant analytes; Real-time q-PCR measured cytokine and PPARβ/δ mRNA expression. cPGI₂, not RGZ, significantly decreased CXCL10 in mDCs and CD4⁺ T cells, reduced TNFα in mDCs, CD4⁺ T and monocytes, and diminished IFNγ in mDCs. IL-10 did not change. cPGI₂-induced CXCL10 downregulation, with TNFα and IFNγ decrease, might be relevant, given its early activity in ARD development. Scenarios on PPARβ/δ agonist re-positioning aimed at modulating CXCL10 might open opportunities to support ARD management and targeted therapy development.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Split Intein-Mediated Engineering of Bacteriocins Through Backbone Circularization, Modular Assembly of Chimeras, and Inducible Circularization.","authors":"Irene Lafuente, Ester Sevillano, Nuria Peña, Cleopatra Collado, Luis M Cintas, Pablo E Hernández, Estefanía Muñoz-Atienza, Juan Borrero","doi":"10.3390/biom16091311","DOIUrl":"10.3390/biom16091311","url":null,"abstract":"<p><p>The increasing prevalence of antimicrobial resistance has renewed interest in bacteriocins and other antimicrobial peptides as promising alternatives to conventional antibiotics. In this context, in vitro cell-free protein synthesis (IV-CFPS) provides a rapid and versatile platform for the production and functional evaluation of bacteriocins, enabling antimicrobial screening without the limitations associated with cellular expression, low production yields, or peptide toxicity. In previous studies, we demonstrated the utility of IV-CFPS for the production and characterization of a broad range of bacteriocins. More recently, integration of IV-CFPS with split intein-mediated ligation (SIML) enabled the production and functional evaluation of circular bacteriocins, thereby expanding the repertoire of bacteriocins accessible to cell-free synthesis and screening. Here, we further expand the capabilities of the IV-CFPS/SIML platform through three complementary bacteriocin engineering strategies. First, SIML was applied to the backbone circularization of naturally linear bacteriocins, demonstrating that SIML-mediated circularization can be extended beyond naturally circular bacteriocins. Second, the platform enabled the modular assembly of chimeric bacteriocins through the ligation of the translocation/receptor-binding (T-R) and cytotoxic (C) domains of either the same or different colicins. Finally, we developed a proof-of-concept inducible protein trans-splicing system in which bacteriocin circularization is triggered by the addition of a complementary split intein component, thereby providing temporal control over peptide activation. These results establish IV-CFPS/SIML as a versatile platform for programmable bacteriocin engineering and substantially expand its applications beyond the production of naturally circular bacteriocins.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panduratin A Induces Caspase-Dependent Apoptosis and G1-Associated Cell-Cycle Arrest and Enhances TNF-α-Associated Cytotoxicity in NSCLC Cells.","authors":"Nitchakarn Phimthong, Jatuporn Polhiran, Saranyapin Potikanond, Wutigri Nimlamool, Nitwara Wikan","doi":"10.3390/biom16091312","DOIUrl":"10.3390/biom16091312","url":null,"abstract":"<p><strong>Background: </strong>Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related mortality. Current therapies are limited by drug resistance and adverse effects, highlighting the need for new strategies. Panduratin A (PA), a chalcone from <i>Boesenbergia rotunda</i>, has reported anticancer activity. This study investigated the effects of PA in NSCLC cells and whether PA enhances tumor necrosis factor alpha (TNF-α)-associated cell death.</p><p><strong>Methods: </strong>Human NSCLC cell lines A549 and H1299 were treated with PA alone or in combination with TNF-α. Cytotoxicity and apoptosis were assessed using cell-viability assays, cell-number analysis, and flow cytometry. Western blotting was used to evaluate caspase-3 activation and PARP-1 cleavage. Cell-cycle distribution was analyzed to determine the impact of PA on cell-cycle progression.</p><p><strong>Results: </strong>PA reduced cell number and induced cell death in both A549 and H1299 cells, and co-treatment with TNF-α increased apoptosis compared with single-agent treatment. PA increased the G1-phase fraction and, in a concentration-dependent manner, reduced expression of thymidine kinase and cyclin A2, consistent with a G1-associated arrest phenotype. Combination treatment also increased the sub-G1 population.</p><p><strong>Conclusions: </strong>PA promotes apoptosis in NSCLC cells and enhances TNF-α-associated apoptotic cell death in vitro, accompanied by a G1-associated cell-cycle phenotype. These findings provide an in vitro framework for studying natural compounds as modulators of TNF-α-driven apoptosis and support further mechanistic validation in more disease-relevant models.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complexation of Polypeptides and Polypeptoids with Nucleic Acids: Does Chirality Matter for Salt Stability and Morphology?","authors":"Kimiasadat Mirlohi, Anuja Thapa, Donghui Zhang, Whitney C Blocher McTigue","doi":"10.3390/biom16091315","DOIUrl":"10.3390/biom16091315","url":null,"abstract":"<p><p>Liquid-liquid phase separation (LLPS), especially via coacervation, offers a novel drug delivery strategy by encapsulating therapeutic agents within phase-separated droplets, thereby improving stability, solubility, and controlled release. Polypeptides and polypeptoids are ideal biomaterials for these systems due to their versatility and tunable properties. Polypeptoids are particularly advantageous, offering enhanced enzymatic resistance and greater control over molecular interactions, making them suitable for complexation studies. This research explores the binary complexation of L-, D,L-, and N-substituted (peptoid) poly-lysine with nucleic acids, specifically two lengths of salmon sperm dsDNA and baker's yeast tRNA, and two nucleotides, adenosine triphosphate (ATP) and cytidine triphosphate (CTP). By adjusting the charge fractions, we studied the morphology of the complexes and tested their salt resistance under different ionic conditions. Results show that dsDNA forms precipitates with lysine polypeptides and polypeptoids, whereas tRNA forms coacervate droplets, likely due to differences in secondary structure. Both nucleotides formed coacervates in all systems. L-homochiral poly-lysine complexes are the most salt-stable, followed by racemic poly-lysine, with N-substituted polymers being the least stable as ionic strength rises. For all dsDNA and tRNA systems, the complexes remained under physiologically relevant salt concentrations. These results highlight the role of salt and polymer structures in modulating complexation. The study offers insights into nucleic acid complexation, with implications for nucleic acid encapsulation and stabilization.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}