Journal of Inorganic Biochemistry最新文献

{"title":"Schiff Base-platinum and ruthenium complexes and anti-Alzheimer properties.","authors":"Salih Günnaz, Esma Yildiz, Ayça Tunçel Oral, Fatma Yurt, Arzum Erdem, Sevil Irişli","doi":"10.1016/j.jinorgbio.2024.112790","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2024.112790","url":null,"abstract":"<p><p>This study investigates the effects of Pt and Ru complexes containing a Schiff base with a diimine structure on Alzheimer's disease. The Schiff base (N1E,N2E)-N1,N2-bis(isoquinolin-4-ylmethylene)benzene-1,2-diamine (I) and the novel Pt(II) and Ru(II) complexes (Ia and Ib) were synthesized and characterized using FTIR, NMR (¹H, ¹³C), mass spectrometry, and elemental analyses. Their ability to inhibit amyloid beta (Aβ_1-42) aggregation was determined in vitro using the SH-SY5Y cell line. Fluorescence spectroscopy investigated the early aggregation kinetics and dose-dependent characteristics of Aβ₁_-₄₂ with the complexes. Transmission electron microscopy confirmed the results. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and ¹H NMR spectroscopy examined the interaction with Aβ₁_-₁₆. Electrochemical analysis using square wave voltammetry monitored the interaction with Aβ₁_-₄₂. The synthesized complexes were active in inhibiting amyloid aggregation at a low molar ratio.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"112790"},"PeriodicalIF":3.8,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765193","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":"Metal (Au, Pt, Pd, Ni) Bis(dithiolene) complexes as dual-action agents combating cancer and trypanosomatid infections.","authors":"Hadi Hachem, Yann Le Gal, Olivier Jeannin, Dominique Lorcy, Gonzalo Scalese, Leticia Pérez-Díaz, Dinorah Gambino, António P Matos, Fernanda Marques","doi":"10.1016/j.jinorgbio.2024.112788","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2024.112788","url":null,"abstract":"<p><p>Cancer and infection diseases pose severe threats to public health worldwide stressing the need for more effective and efficient treatments. Thus, the search for broad-spectrum activity drugs seems justifiable and urgent. Herein, we investigate the anticancer and antitrypanosomatid (anti-Trypanosoma cruzi) activities of eight monoanionic metal bis(dithiolene) complexes, [Ph₄P][M(R-thiazdt)₂] with Mⁿ⁺ = Au³⁺, Pt²⁺, Pd²⁺, Ni²⁺, containing N-alkyl-1,3-thiazoline-2-thione dithiolene ligands (R-thiazdt) with different alkyl groups (R = Et, tBu). Compared to auranofin (AF) and cisplatin (CP), two reference drugs in clinical use, all complexes showed high anticancer activities against A2780 ovarian cancer cells (IC₅₀ values of 0.6-3.8 μM) some also being able to overcome CP resistance in A2780cisR cells. The selectivity index (SI), the IC₅₀ values on normal cells (HDF) vs. A2780 cells, indicated good anticancer specificity (SI > 3) for most of the complexes but with clinical relevance for [Ph₄P][Pd(tBu-thiazdt)₂] (SI = 10). All complexes showed relevant antitrypanosomatid activities (IC₅₀ values of 2.6-5.8 μM) some even exhibiting lower IC₅₀ values than the reference drug nifurtimox (NFX). The mechanism of cell death seemed to be mediated mainly by the formation of reactive oxygen species (ROS), although to lesser extent for the gold complexes but superior to AF. Although ROS play a role in the main apoptotic pathways, cell death by apoptosis was not evident as shown by the caspase-3/7 assay and the morphological cell features studies by electron microscopy (SEM). Results obtained evidenced that [Ph₄P][Pt(tBu-thiazdt)₂] and [Ph₄P][Pd(tBu-thiazdt)₂] complexes might have potential as novel anticancer and antitrypanosomatid agents as alternatives to current therapeutics.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"112788"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790897","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":"Interaction of V^VO₂-hydrazonates with lysozyme.","authors":"Maddalena Paolillo, Giarita Ferraro, Gurunath Sahu, Pratikshya Das Pattanayak, Eugenio Garribba, Sourangshu Halder, Riya Ghosh, Bipul Mondal, Pabitra B Chatterjee, Rupam Dinda, Antonello Merlino","doi":"10.1016/j.jinorgbio.2024.112787","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2024.112787","url":null,"abstract":"<p><p>Vanadium compounds (VCs) exhibit a broad range of pharmacological properties, with their most significant medical applications being in the treatment of cancer and diabetes. The therapeutic effects and mode of action of VCs may be associated with their ability to bind proteins and, consequently, understanding the VC-protein interaction is of paramount importance. Among the promising VCs, the V^VO₂ complex with the aroylhydrazone furan-2-carboxylic acid ((3-ethoxy-2-hydroxybenzylidene)hydrazide, hereafter denoted as VC1), deserves attention, since it exhibits cytotoxicity against various cancer cell lines, including HeLa. The interaction between VC1 and its analogue, denoted as VC2 (the dioxidovanadium(V) complex with (E)-N'-(1-(2-hydroxy-5-methoxyphenyl)ethylidene)furan-2-carbohydrazide), and hen egg white lysozyme (HEWL) was examined by UV-vis spectroscopy, fluorescence, circular dichroism, and X-ray crystallography. The interaction of VC1 and VC2 with HEWL does not alter the protein secondary and tertiary structure. Crystallographic studies indicate that the two metal complexes or V-containing fragments originating from VC1 and VC2 bind the protein via non-covalent interactions. Furthermore, when bound to HEWL, two VC1 molecules and two VC2 molecules form a supramolecular association stabilized by stacking interactions. This type of interaction could favour the binding of similar compounds to proteins and affect their biological activity.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"112787"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790867","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":"Co(II), Cu(II), and Zn(II) thio-bis(benzimidazole) complexes induce apoptosis via mitochondrial pathway.","authors":"Peter Antal, Juraj Kuchár, Luca Rigamonti, Marie Kvasnicová, Gabriel Gonzalez, Lucie Rárová, Miroslav Strnad, Pavel Kopel","doi":"10.1016/j.jinorgbio.2024.112786","DOIUrl":"https://doi.org/10.1016/j.jinorgbio.2024.112786","url":null,"abstract":"<p><p>The copper(II), cobalt(II), and zinc(II) complexes with 2-(1H-benzimidazol-2-ylmethylsulfanylmethyl)-1H-benzimidazole (tbb) and 2-[2-[2-(1H-benzimidazol-2-yl)ethylsulfanyl]ethyl]-1H-benzimidazole (tebb), [Cu(tbb)Cl₂] (1), [Co(tbb)Cl₂] (2), [Zn(tbb)Cl₂] (3), [Cu(tebb)Cl(H₂O)]Cl (4), [Co(tebb)Cl₂]_n·nCH₃OH (5) and [Zn(tebb)Cl(H₂O)]Cl (6), have been prepared and evaluated for antiproliferative activity. The structure of (4) was proved by X-ray diffraction crystallography. The coordination compounds were tested for their cytotoxic activities in cancer cell lines in vitro. The lower IC₅₀ values were obtained for Co(II), Cu(II), and Zn(II) complexes with tebb in comparison with tbb complexes. Complex 2 showed strong antiproliferative selectivity for leukemia CEM cells and nontoxicity towards other tested cell lines and normal human cells (BJ and RPE-1). Proapoptotic activity of 2 and 5 were weaker than positive control cisplatin, but the big advantage of these complexes was their zero-cytotoxicity for normal healthy cells in contrast to the high cytotoxicity of cisplatin. The activation of apoptotic initiation phase was detected in neuroblastoma cancer cell line SH-SY5Y where 5 was cytotoxic without fragmentation of cells. Interestingly, complexes 5, 6, and tebb, together with cisplatin, dramatically impaired the mitochondrial membrane potential of SH-SY5Y after 72 h. Taken together, we demonstrated that our compounds trigger apoptosis via the mitochondrial pathway.</p>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"112786"},"PeriodicalIF":3.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790824","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":"Nitroxidative stress in human neural progenitor cells: In situ measurement of nitric oxide/peroxynitrite imbalance using metalloporphyrin nanosensors","authors":"Nouf Alsiraey ,&nbsp;Howard D. Dewald","doi":"10.1016/j.jinorgbio.2024.112785","DOIUrl":"10.1016/j.jinorgbio.2024.112785","url":null,"abstract":"<div><div>Nitric oxide (NO) is an essential inorganic signaling molecule produced by constitutive NO synthase (cNOS) in the neurological system. Under pathological conditions, NO rapidly reacts with superoxide (O₂^•−) to generate peroxynitrite (ONOO^¯). Elevated ONOO^¯ concentrations induce nitroxidative stress, potentially contributing to numerous pathological processes as observed in neurodegenerative diseases including Alzheimer's disease (AD). Metalloporphyrin nanosensors, (200<span><math><mo>–</mo></math></span>300 nm diameter), were applied to quantify the NO/ONOO^¯ balance produced by a single human neural progenitor cell (hNPC), <em>in situ</em>. These nanosensors, positioned in proximity of 4<span><math><mo>–</mo></math></span>5 ± 1 μm from the hNPCs membrane, enabled real-time measurement of NO and ONOO^¯ concentrations following calcium ionophore (CaI) stimulation. The ratio of NO to ONOO^¯ concentration ([NO]/[ONOO^¯]) was established for the purpose of quantifying nitroxidative stress levels. Normal hNPCs produced a maximum of 107 ± 1 nmol/L of NO and 451 ± 7 nmol/L of ONOO^¯, yielding a [NO]/[ONOO^¯] ratio of 0.25 ± 0.005. In contrast, the model of the dysfunctional hNPCs, for long-term (48 h) amyloid-beta 42 (Aβ₄₂) exposure significantly altered NO/ONOO^¯ production. The NO level decreased to 14 ± 0.1 nmol/L, while ONOO^¯ increased to 843 ± 0.8 nmol/L, resulting in a 94 % reduction of the [NO]/[ONOO^¯] ratio to 0.016 ± 0.0001. The [NO]/[ONOO^¯] ratio is determined by this work as a possible biomarker of nNOS efficiency and hNPC dysfunction, with implications for neurodegenerative disorders such as AD. Promising applications in the early medical diagnosis of neurological illnesses, electrochemical metalloporphyrin nanosensors demonstrate efficacy in real-time nitroxidative stress monitoring.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"263 ","pages":"Article 112785"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699527","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":"Effects of structurally varied fluorescent half-sandwich iridium(III) Schiff base complexes on A549 cell line","authors":"Xicheng Liu,&nbsp;Changjian Ji,&nbsp;Rui Tao,&nbsp;Wenya Zheng,&nbsp;Mengxian Liu,&nbsp;Shiqing Bi,&nbsp;Qinghua Chang,&nbsp;Xiang-Ai Yuan,&nbsp;Mingbo Yue,&nbsp;Zhe Liu","doi":"10.1016/j.jinorgbio.2024.112792","DOIUrl":"10.1016/j.jinorgbio.2024.112792","url":null,"abstract":"<div><div>Half-sandwich iridium(III) (Ir^III) anticancer complexes, as promising alternatives to platinum-based drugs, especially for solving resistance to platinum drugs, have demonstrated excellent application prospect. The potency of these Ir^III complexes as anticancer agents could be significantly enhanced through the strategic modification of their peripheral ligands. In this study, four structurally varied triphenylamine (TPA)-modified half-sandwich Ir^III Schiff base complexes were designed and prepared. The incorporation of TPA unit has effectively endowed these complexes with suitable emission, which facilitates the evaluation of intracellular accumulation and cell morphology. These complexes demonstrated favorable in vitro anti-proliferative activity against A549 cell line (lung cancer cells, derived from alveolar basal epithelial cells), especially for pentamethylcyclopentadiene (Cp*)-based one (<strong>IrTS1</strong> and <strong>IrTS3</strong>), and that is almost 2.5-fold more than cisplatin under the same conditions. Meanwhile, <strong>IrTS1</strong> and <strong>IrTS3</strong> possessed excellent activity against A549/DDP (cisplatin-resistant) cell line and the similar cytotoxicity to cisplatin against BEAS-2B cell line (derived from the bronchial epithelium of normal human lungs), then following a mitochondria apoptotic channel.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"263 ","pages":"Article 112792"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745724","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":"Copper(II) complex with 1-allylimidazole induces G2/M cell cycle arrest and suppresses A549 cancer cell growth by attenuating Wnt, JAK-STAT, and TGF-β signaling pathways","authors":"Katarzyna Gałczyńska ,&nbsp;Aneta Węgierek-Ciuk ,&nbsp;Katarzyna Durlik-Popińska ,&nbsp;Paulina Żarnowiec ,&nbsp;Krystyna Kurdziel ,&nbsp;Michał Arabski","doi":"10.1016/j.jinorgbio.2024.112791","DOIUrl":"10.1016/j.jinorgbio.2024.112791","url":null,"abstract":"<div><div>The main aim of the study was to investigate the molecular mechanism of action of the potentially anti-cancer agent copper(II) complex with 1-allylimidazole [Cu(1-allim)₄(NO₃)₂] using the A549 lung cancer line, toward which it is selectively cytotoxic. Gene expression analysis showed that the complex caused apoptosis through WNT, JAK-STAT, and TGF-β pathways. The complex induced DNA damage, ROS production, and depolarization of the mitochondrial membrane, suggesting that its toxicity is likely due to induction of the intrinsic apoptosis pathway. It also arrested the cell cycle at G2/M phase. Particularly noteworthy is that it inhibited the WNT pathway, a target for lung cancer therapies. Its complex mechanism of action may hinder the acquisition of immunity by cancer cells.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112791"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743580","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":"Positively-charged, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes functionalized with ethacrynic acid: Synthesis, characterizaion, and antitumor effect","authors":"Yuxin Xuan ,&nbsp;Yuxi Yan ,&nbsp;Xiaonan Wei,&nbsp;Shuxiang Wang,&nbsp;Jinchao Zhang,&nbsp;Yonghe Tang,&nbsp;Shenghui Li","doi":"10.1016/j.jinorgbio.2024.112778","DOIUrl":"10.1016/j.jinorgbio.2024.112778","url":null,"abstract":"<div><div>A new family of ethacrynic acid-functionalized, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes (<strong>4a-4e</strong>) have been designed, synthesis and fully characterized by ¹H and ¹³C NMR, ESI-MS, elemental analysis, and melting point tests. The molecular structure of <strong>3a</strong>, one of the precursor complexes, has been determined by single-crystal X-ray diffraction. The cytotoxicity of the obtained complexes toward human cancer cell lines such as HeLa, MGC803, A549, MDA-MB-231, and MCF-7 cells have been investigated by MTT assay. Whereas complexes <strong>4d</strong> and <strong>4e</strong> showed significantly higher cytotoxicity than cisplatin (the positive control group) and complexes <strong>3a-3e</strong>. Moreover, complexes <strong>4d</strong> and <strong>4e</strong> exhibited a certain selectivity (selectivity index: 7.33 and 7.57) toward MCF-7 cells over MCF-10a normal cells. Glutathione <em>S</em>-transferases (GSTs) activity assay indicate that complexes <strong>4d</strong> and <strong>4e</strong> exhibited higher GST inhibitory activity than ethacrynic acid (EA, the best characterized GST inhibitor), consistent with their higher cytotoxicity. Further mechanistic studies showed that <strong>4e</strong>-induced cell apoptosis may be aroused by the production of ROS, the loss of mitochondrial membrane potential and G2/M phase cell arrest in MCF-7 cells. In addition, the <em>in vivo</em> antitumor effect study on the xenograft mouse models of MCF-7 cells reveal that complex <strong>4e</strong> significantly inhibited tumor growth with a higher inhibition efficiency of 68.80 %, in comparison with the groups treated with cisplatin (59.25 %). These results highlight the strong possibility to develop positively-charged, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes funcionalized with GST inhibitor as promising anticancer agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"263 ","pages":"Article 112778"},"PeriodicalIF":3.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745722","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":"Expanding the scope of copper artificial metalloenzymes: A potential fluorinase?","authors":"Isabeau Lüddecke,&nbsp;Amanda G. Jarvis","doi":"10.1016/j.jinorgbio.2024.112777","DOIUrl":"10.1016/j.jinorgbio.2024.112777","url":null,"abstract":"<div><div>Biocatalysts for fluorination are rare, and thus of great interest for artificial enzyme design. Biohybrid catalysts including Cu-based DNAzymes and dinucleotide catalysts can catalyse enantioselective electrophilic fluorination of β-ketoesters. Here we report the investigation of Cu-based artificial metalloenzymes as catalysts for electrophilic fluorination reactions. A library of artificial copper proteins was prepared by bioconjugation of bidentate and tridentate nitrogen ligands to cysteine variants of the Sterol Carrier Protein 2 L (SCP-2 L) and subsequent addition of Cu(II) salts. The resulting copper proteins were screened for activity for the fluorination of β-ketoesters using Selectfluor. Under aqueous acidic conditions it was observed that the designed catalysts did not outcompete the uncatalysed background reaction. This work highlights that careful consideration of substrate reactivity and background reactions is needed when considering potential reactions for artificial metalloenzyme catalysis.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"263 ","pages":"Article 112777"},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemin, copper and amyloid-β: A medley involved in Alzheimer's disease. An interaction that fine regulates the reactivity","authors":"Chiara Bacchella ,&nbsp;Silvia De Caro ,&nbsp;Stefania Nicolis ,&nbsp;Enrico Monzani ,&nbsp;Simone Dell'Acqua","doi":"10.1016/j.jinorgbio.2024.112775","DOIUrl":"10.1016/j.jinorgbio.2024.112775","url":null,"abstract":"<div><div>Metal ions have been shown to play a critical role in amyloid-β (Aβ) neurotoxicity and plaque formation which are key hallmarks of Alzheimer's disease. Amyloid-β peptides can bind both copper and hemin and this interaction modulates the redox chemistry of these metals. The characterization of the binding of hemin through UV–Vis spectroscopic titration with Aβ(4-16) shows a significantly higher affinity than that with Aβ(1-16). Also, the characterization of the hemin-catalyzed oxidation through different assays (peroxidase-like activity, ascorbate oxidation, HPLC-MS analysis of peptide oxidation) displays a greater reactivity in the presence of Aβ(4-16) when compared to that of Aβ(1-16). Since the Aβ(4-16) peptide sequence contains the typical amino-terminal copper and nickel binding motif (ATCUN), this leads to investigate the potential formation of ternary hemin/copper/Aβ(4-16) adducts. The evaluation of K₁ and K₂ (constants that regulate the formation of five-coordinated high-spin complex and of six-coordinated low-spin complex, respectively) for mixed systems indicates that the presence of copper stabilizes the 1:1 hemin-Aβ(4-16) species, partially hindering the formation of the low-spin complex. On the other hand, the formation of the ternary hemin/copper/Aβ(4-16) complex gives rise to a less efficient catalyst, resulting in a reduction of the overall oxidative reactivity. These results suggest that the reactivity of metal ions is finely modulated by the formation of complexes with amyloid peptides and this property is also regulated differently by the various in vivo relevant isoforms.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"263 ","pages":"Article 112775"},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}