Journal of Inorganic Biochemistry最新文献

{"title":"Design, synthesis, and antitumor mechanism investigation of iridium(III)/ruthenium(II)-vadimezan conjugates towards 4T1 cells","authors":"Yong-Sheng Yang ,&nbsp;Hou Zhu ,&nbsp;Chun-Rong Jiang,&nbsp;Zheng Zhang,&nbsp;Meng-Ting Xu,&nbsp;Rong-Tao Li,&nbsp;Rui-Rong Ye","doi":"10.1016/j.jinorgbio.2026.113241","DOIUrl":"10.1016/j.jinorgbio.2026.113241","url":null,"abstract":"<div><div>Transition metal iridium(III) and ruthenium(II) complexes exhibit significant anti-tumor potential. Vadimezan (VDA) is a potent non-nucleotide stimulator of interferon genes (STING) agonist that enhances the efficacy of tumor immunotherapy. Herein, we designed and synthesized three iridium(III) (<strong>Ir-VDA-1</strong>–<strong>3</strong>, C^N = 2-phenylpyridine (ppy, in <strong>Ir-VDA-1</strong>), 2-(2-thienyl)pyridine (thpy, in <strong>Ir-VDA-2</strong>), and 2-(2,4-difluorophenyl)pyridine (dfppy, in <strong>Ir-VDA-3</strong>)) and three ruthenium(II) (<strong>Ru-VDA-1</strong>–<strong>3</strong>, N^N = 4,7-diphenyl-1,10-phenanthroline (DIP, in <strong>Ru-VDA-1</strong>), 1,10-phenanthroline (phen, in <strong>Ru-VDA-2</strong>), and 2,2′-bipyridine (bpy, in <strong>Ru-VDA-3</strong>)) complexes by incorporating VDA with iridium(III) and ruthenium(II) complexes. Among of these, <strong>Ir-VDA-1</strong>–<strong>3</strong> exhibited potent antitumor activity. <strong>Ir-VDA-1</strong>–<strong>3</strong> were effectively internalized by mouse triple negative breast cancer (TNBC) 4T1 cells and localized to mitochondria, inducing mitochondrial pathway-mediated apoptosis. Western blot analysis revealed that <strong>Ir-VDA-1</strong>–<strong>3</strong> activated and cleaved caspase 3, subsequently cleaving GSDME to induce pyroptosis. Notably, <strong>Ir-VDA-1</strong>–<strong>3</strong> treatment significantly upregulated the expression of key proteins (cyclic GMP-AMP synthase (cGAS) and phosphorylated STING (p-STING)) in the cGAS-STING signaling pathway. Furthermore, <strong>Ir-VDA-1</strong>–<strong>3</strong> functioned as the immunogenic cell death (ICD) inducers, promoting damage-associated molecular patterns (DAMPs) release, including calreticulin (CRT), high mobility group protein 1 (HMGB1), and adenosine triphosphate (ATP). This strategy provides a novel design concept for multimodal synergistic cancer therapy.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"278 ","pages":"Article 113241"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactoperoxidase: Identification of the two Tyr radical sites for the stabilization of the pH-dependent [Fe(IV) = O Tyr•] catalytic intermediates by resonance Raman and multifrequency Electron Paramagnetic Resonance spectroscopies","authors":"Piotr J. Mak ,&nbsp;Sandra Acebes ,&nbsp;Victor Guallar ,&nbsp;James R. Kincaid ,&nbsp;Anabella Ivancich","doi":"10.1016/j.jinorgbio.2025.113199","DOIUrl":"10.1016/j.jinorgbio.2025.113199","url":null,"abstract":"<div><div>We have fully characterized the high-valent intermediates formed during the catalytic cycle of lactoperoxidase (LPO), a heme-containing enzyme present in milk, saliva, tears and airways, playing an important role in mammalian antimicrobial defense. Our combined approach of multifrequency (9–285 GHz) Electron Paramagnetic Resonance (EPR) and resonance Raman (rR) spectroscopies allowed the identification of Tyr21 and Tyr193 as radical sites, having a concerted role with the heme iron and resulting in two distinct [Fe(IV) = O Tyr^•] intermediates in LPO's catalytic cycle. The presence and strength of H-bonds to Tyr^• assessed by the C − O stretching mode (v_7a) and the gx component of the g-tensor detected in their rR and 285-GHz EPR spectra, respectively, induced a difference in pH-dependent stabilization of the [Fe(IV) = O Tyr₂₁^•] and [Fe(IV) = O Tyr₁₉₃^•] intermediates. The later resulted from single-step electron tunneling subsequent to the formation of the [Fe(IV) = O Por^•+] species. A Trp radical contributing to the LPO 285-GHz EPR spectra, discern by the advantageous resolution of g-values, is proposed to facilitate the electron transfer to Tyr193. Our computational analysis (PELE) crucially identified a unique surface binding site for 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), close to Tyr21 (shown to host the spin by QM/MM simulations), thus consistent with LPO Tyr^• pH 5.6 detected in the rR and 285-GHz EPR spectra and the substrate oxidation previously shown by our UV–Vis stopped flow electronic absorption studies. The elucidation of the catalytic electron transfer pathways and the protein-based oxidizing sites is relevant to harnessing the concerted reactivity of heme and specific Tyr/Trp sites in natural biocatalysts.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113199"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin modulates Aβ1–42 aggregation toward non-toxic forms: A comparative study with cis-[Ru(phen)2(3,4Apy)2]2+","authors":"Marco A. Tiburcio ,&nbsp;Bárbara Patrícia N. Silva ,&nbsp;Maria Laura da C. Garcia ,&nbsp;Lorena M.B. Pereira ,&nbsp;Marina M. Grigoli ,&nbsp;Márcia R. Cominetti ,&nbsp;Rose M. Carlos","doi":"10.1016/j.jinorgbio.2026.113225","DOIUrl":"10.1016/j.jinorgbio.2026.113225","url":null,"abstract":"<div><div>Intranasal insulin therapy for Alzheimer's disease (AD) has received increasing attention due to its potential to modulate amyloid-β (Aβ) aggregation, a hallmark of AD pathology. <strong>Molecular dynamics simulations suggest that insulin binds across U-shaped Aβ</strong>_{<strong>1</strong>}_{<strong>–</strong>}_{<strong>42</strong>} <strong>oligomers, disrupting β-strand alignment via its A-chain. In contrast, the Ru(II) complex <em>cis</em>-[Ru(phen)</strong>_{<strong>2</strong>}<strong>(3,4Apy)₂]</strong>^{<strong>2+</strong>} <strong>(Ru3,4Apy; phen = 1,10-phenanthroline; 3,4Apy = 3,4-aminopyridine) primarily interacts with fibril surfaces. Although both target the central hydrophobic core motif, they bind to distinct regions of Aβ</strong>_{<strong>1</strong>}_{<strong>–</strong>}_{<strong>42</strong>}<strong>.</strong> Their co-aggregation with Aβ₁_–₄₂ may thus influence aggregation and cytotoxicity differently, providing insight into <strong>the molecular mechanisms underlying insulin's mitigation of Aβ-induced cytotoxicity</strong>. We monitored Aβ₁_–₄₂ aggregation using Tyr10 intrinsic fluorescence, circular dichroism, atomic force microscopy, and SH-SY5Y cell viability assays in the presence of insulin, Ru3,4Apy, or both. Ru3,4Apy reduced β-sheet formation but did not prevent <strong>Aβ</strong>_{<strong>1</strong>}_{<strong>–</strong>}_{<strong>42</strong>}<strong>-induced cytotoxicity</strong>. In contrast, insulin limited conformational flexibility, prevented Tyr10 burial, suppressed β-sheet formation, and promoted amorphous, non-toxic aggregates. Notable, in the Aβ₁_–₄₂/Ru3,4Apy/Insulin mixture, aggregation followed a non-toxic pathway bypassing the buried-core β-sheet typical of mature fibrils. These findings emphasize the specificity of Aβ₁_–₄₂/Insulin interactions and suggest targeting defined binding sites as a promising AD therapeutic strategy.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113225"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal anticancer potential of newly synthesized palladium(II), platinum(II), and gold(III) complexes with 2-(Thiazol-2-yl)pyridine-4,5-dicarboxylate dimethyl ester","authors":"Tina P. Andrejević ,&nbsp;Jakob Kljun ,&nbsp;Sanja Matić ,&nbsp;Tijana Marković ,&nbsp;Žiko Milanović ,&nbsp;Kristina Milisavljević ,&nbsp;Darko P. Ašanin ,&nbsp;Suzana Popović ,&nbsp;Dejan Baskić ,&nbsp;Iztok Turel ,&nbsp;Miloš I. Djuran ,&nbsp;Biljana Đ. Glišić","doi":"10.1016/j.jinorgbio.2025.113208","DOIUrl":"10.1016/j.jinorgbio.2025.113208","url":null,"abstract":"<div><div>Novel palladium(II), platinum(II), and gold(III) complexes, [PdCl₂(py-2tz)] (<strong>1</strong>), [PtCl₂(py-2tz)] (<strong>2</strong>), and [AuCl₂(py-2tz)][AuCl₄] (<strong>3</strong>), py-2tz is 2-(Thiazol-2-yl)pyridine-4,5-dicarboxylate dimethyl ester, were synthesized and characterized using spectroscopy (¹H and ¹³C NMR, IR, and UV–Vis), mass spectrometry, density functional theory (DFT), electrochemical (cyclic voltammetry), and crystallographic methods. Single-crystal X-ray diffraction analysis revealed that all complexes are square-planar with bidentate coordination of the py-2tz ligand <em>via</em> its pyridine and thiazole nitrogen atoms to the corresponding metal ion. These complexes were further evaluated against three human cell lines, two cancer (colon, HCT-116, and cervical adenocarcinoma, HeLa) and one healthy (embryonic lung fibroblast, MRC-5), using the MTT cytotoxicity assay. The influence of these complexes on the type of cell death and cell cycle progression were examined by flow cytometry. Of all the complexes investigated, the gold(III) complex showed the most prominent cytotoxicity toward tumor cells, with reduced toxicity against MRC-5 compared to cisplatin. Furthermore, this complex induced apoptosis and autophagy in both tumor cell lines, and G2/M arrest in HCT-116 cells. The binding interactions of the complexes <strong>1</strong>–<strong>3</strong> with bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) were also investigated using fluorescence spectroscopy, complemented by molecular docking simulations.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113208"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polypyridyl Ru(II) tamoxifen analogues: Estrogen receptor-targeted dual photodynamic and chemotherapeutic agents","authors":"Guillermo Moreno-Alcántar ,&nbsp;Claudia Schmidt ,&nbsp;Darren Dennis Wragg ,&nbsp;Riccardo Scotti ,&nbsp;Iñigo Iribarren Aguirre ,&nbsp;Riccardo Bonsignore ,&nbsp;Angela Casini ,&nbsp;Denise Lovison","doi":"10.1016/j.jinorgbio.2025.113202","DOIUrl":"10.1016/j.jinorgbio.2025.113202","url":null,"abstract":"<div><div>The use of targeted chemotherapeutic agents and of locally active treatments such as photodynamic therapy (PDT), are strategies to tackle the side effects and enhance the effectiveness of anticancer treatments. In this context, the development of multifunctional drugs, which combine targeted chemotherapy and photosensitizing capabilities, has garnered increased attention. Herein, we introduce two polypyridyl ruthenium(II) compounds featuring tamoxifen-related ligands (<strong>RuTamOMe</strong> and <strong>RuTamOH</strong>) targeting the estrogen receptor α (ERα) and able to generate singlet oxygen via energy transfer. The compounds display enhanced phototoxicity, tested in different cell lines (A375 melanoma, MDA-MB-231 triple negative adenocarcinoma and MCF-7 ER+ breast cancer cells) and examined in terms of the ERα expression dependence. Computational studies were also performed, corroborating the suitability of the compounds to target ER, maintaining tamoxifen's affinity for the receptor binding site, and revealing a minimal influence of the stereochemical configuration of the compounds on their targeting capabilities. Altogether, our results highlight the potential of <em>hybrid</em> Ru(II) polypyridyl compounds as suitable platforms for generating targeted metallodrugs with photosensitizing capabilities.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113202"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoester hydrolysis using a de novo designed protein: A combined experimental and computational study","authors":"Dona Imanga Upamadi Edirisinghe ,&nbsp;Prerana Dash ,&nbsp;Jiawen Yang ,&nbsp;Sreerag N. Moorkkannur ,&nbsp;Deepa Neupane ,&nbsp;Jithma Gethmini Piyasara Sriwardana Dissanayake ,&nbsp;Alexis Eckhart ,&nbsp;Katlyn Meier ,&nbsp;Rajeev Prabhakar ,&nbsp;Olga V. Makhlynets","doi":"10.1016/j.jinorgbio.2026.113215","DOIUrl":"10.1016/j.jinorgbio.2026.113215","url":null,"abstract":"<div><div>Metallohydrolases use metal cations in their active sites to catalyze the hydrolytic cleavage of biological substrates. We used a simple model protein Due Ferri single chain (DFsc) in combination with Mn-Mn and Zn-Zn to study the effect of the nature of metal ions on its reactivity. The ICP-OES analysis confirmed the metal ion binding with desired ratios. The Mn₂-DFsc showed the highest hydrolytic activity with a catalytic efficiency (k_cat/K_m) of 6.5 M⁻¹ min⁻¹. EPR analysis of the di‑manganese DFsc indicates that two manganese centers are antiferromagnetically coupled in a S = 0 ground state. Based on both experimental and computational results, a mechanism of phosphoester hydrolysis is proposed, in which the substrate binds to Mn terminally, and follows an associative/dissociative mechanism with hydrolysis assisted by nucleophilic attack of the bridging OH nucleophile. The findings from this study can be used to further optimize the DFsc scaffold for designing artificial enzymes for bioremediation of multiple hazardous molecules.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113215"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a novel binuclear copper complex for enhanced cellular copper uptake and cancer treatment","authors":"Haoran Liu ,&nbsp;Jingyi Zhang ,&nbsp;Yanping Li ,&nbsp;Jiamin Jin ,&nbsp;Jian Chen ,&nbsp;Juzheng Zhang","doi":"10.1016/j.jinorgbio.2025.113206","DOIUrl":"10.1016/j.jinorgbio.2025.113206","url":null,"abstract":"<div><div>Although elesclomol (Es) has been investigated as a copper ionophore in antitumor clinical trials, its therapeutic potential remains limited by suboptimal copper transport efficiency and a narrow mechanism of action. To overcome these limitations and improve the anticancer efficacy of copper ionophores, we designed and synthesized L1—a novel chelator capable of forming the binuclear copper complex C1. Our results demonstrate that C1 exhibits superior therapeutic properties compared to Elesclomol–Cu (Es<img>Cu), including enhanced cellular copper uptake in gastric cancer cells and multiple anticancer mechanisms. These mechanisms include potent induction of cuproptosis (significantly stronger than Es<img>Cu), generation of mitochondrial superoxide and intracellular reactive oxygen species, induction of autophagic lysosome accumulation, DNA damage, and activation of apoptosis. More importantly, <em>in vivo</em> studies revealed a remarkable tumor inhibition rate of 80.3 % for C1, substantially higher than that of Es<img>Cu (45 %). These findings establish C1 as a promising next-generation copper-based anticancer agent with enhanced therapeutic potential.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113206"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery, crystal structure, anticancer property of the first-row transition metal complexes of norcantharidin (NCTD) as potential inducer of mitochondrial damage","authors":"Yun-hou Huang ,&nbsp;Yuan Liu ,&nbsp;Yue Huang ,&nbsp;Wei-ying Meng ,&nbsp;Hong-zu Wei ,&nbsp;Chang-chun Wen ,&nbsp;Li-min Liu ,&nbsp;Yan-cheng Liu","doi":"10.1016/j.jinorgbio.2026.113228","DOIUrl":"10.1016/j.jinorgbio.2026.113228","url":null,"abstract":"<div><div>Norcantharidin (<strong>NCTD</strong>) is a structurally modified derivative of cantharidin, which is an active component derived from traditional Chinese medicine (TCM) and exhibiting specific anticancer activity. In this work, four pH-sensitive complexes of <strong>NCTD</strong>, with cationic 2-aminopyridine (<strong>AP</strong>) as the counter ion, were successfully synthesized and structurally characterized. The crystal structures resolved by single crystal X-ray diffraction analysis demonstrated that they all formed in complexes with ionic type, <strong>2AP[M(NCTD)</strong>_{<strong>2</strong>}<strong>]</strong>, (<strong>M</strong> = <strong>Cu</strong>, <strong>Co</strong>, <strong>Ni</strong> and <strong>Mn</strong>), composed of the negative divalent six-coordinated species, <strong>[M(NCTD)</strong>_{<strong>2</strong>}<strong>]</strong>^{<strong>2−</strong>}, and two counter cations (<strong>AP</strong>). Our findings demonstrated that under slightly acidic conditions (pH = 6.6), the decomposition of <strong>2AP[M(NCTD)</strong>_{<strong>2</strong>}<strong>]</strong> (M = Cu, Co, Ni, and Mn) led to the release of <strong>NCTD</strong> and metal ions, which subsequently triggered a Fenton-like reaction co-catalyzed by GSH. They exhibited stronger <em>in vitro</em> anticancer properties than <strong>NCTD</strong> against a series of typical cancer cell lines tested, with the IC₅₀ values in the range of 12.41–33.43 μM, in which <strong>2AP[Cu(NCTD)</strong>_{<strong>2</strong>}<strong>]</strong>, showed the best efficacy. In the most sensitive SK-OV-3 cells, <strong>2AP[Cu(NCTD)</strong>_{<strong>2</strong>}<strong>]</strong>, induced mitochondrial dysfunction by triggering the excessive accumulation of ROS within mitochondria, thereby activating the apoptotic pathway. Meanwhile, <strong>2AP[Cu(NCTD)</strong>_{<strong>2</strong>}<strong>]</strong>, could obviously arrest the cell cycle at Sub-G₁ phase in SK-OV-3 cells.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113228"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The oxygen sensitivity of [4Fe-4S] clusters on the nitrogenase scaffold protein NifU","authors":"Trevor D. Rapson ,&nbsp;Xueqin Wang ,&nbsp;Jessica K. Bilyj ,&nbsp;Christina M. Gregg ,&nbsp;Ingrid Venables ,&nbsp;Anu Mathew ,&nbsp;Julien Langley ,&nbsp;Nicholas Cox ,&nbsp;Guy N.L. Jameson ,&nbsp;Craig C. Wood","doi":"10.1016/j.jinorgbio.2026.113224","DOIUrl":"10.1016/j.jinorgbio.2026.113224","url":null,"abstract":"<div><div>The extreme oxygen sensitivity of nitrogenase enzymes poses a major obstacle to their use in biotechnology, particularly in engineering nitrogen-fixing plants. While the vulnerability of nitrogenase components NifH and NifDK to oxygen is well established, the sensitivity of the metal clusters on scaffold proteins involved in nitrogenase biosynthesis has not been previously reported. In this study, we investigate the oxygen sensitivity of the [4Fe-4S] clusters on the scaffold protein NifU, which supplies these clusters to several downstream targets, including NifH. Using UV/Vis, Mössbauer, and Electron Paramagnetic Resonance (EPR) spectroscopy, we show that exposure to oxygen converts the [4Fe-4S] clusters into [2Fe-2S] clusters. This degradation occurs rapidly, even at low oxygen levels (2 %). However, a fraction of the [4Fe-4S] clusters remain intact under these conditions, allowing NifU to activate apo-NifH by transferring functional clusters. In contrast, at atmospheric oxygen levels (21 %), all [4Fe-4S] clusters are damaged over 10 min, and NifU quickly loses its ability to reactivate apo-NifH.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113224"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxaliplatin-artesunate conjugate intensifies suppression on colorectal cancer by boosting antitumor immunity","authors":"Yehong Tan ,&nbsp;Tao Yang ,&nbsp;Siran Jiang ,&nbsp;Shumeng Li ,&nbsp;Linxiang Cai ,&nbsp;Ying Wang ,&nbsp;Zijian Guo ,&nbsp;Xiaoyong Wang","doi":"10.1016/j.jinorgbio.2026.113212","DOIUrl":"10.1016/j.jinorgbio.2026.113212","url":null,"abstract":"<div><div>Immunosuppressive tumor microenvironment is the major obstacle for antitumor immunotherapy. Elimination of myeloid-derived suppressor cells (MDSCs) potentiates immunotherapy for various solid tumors. Oxaliplatin-artesunate complex OPA decreases MDSCs by inhibiting CD33 and the triggering receptor expressed on myeloid cells 2 (TREM2) in the TME, and enhancing dendritic cell maturation due to its ability to facilitate immunogenic cell death and activate the cyclic-GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway. Moreover, OPA upregulates the costimulatory molecule CD28 and downregulates the immune checkpoint cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on T cells, thus impeding the T cell depletion and immunosuppression. The activation of immune circulation and immunosignal pathway increases the chemotherapeutic activity of parent oxaliplatin. In addition, OPA serves as a cancer vaccine to inhibit tumor metastasis and reoccurrence. Lastly, the stability and safety profiles are superior to that of oxaliplatin. OPA is a unique chemoimmunotherapeutic agent with a distinct mechanism of action and prominent efficacy on orthotopic colorectal cancer in mouse models.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"277 ","pages":"Article 113212"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}