Journal of Inorganic Biochemistry最新文献_第4页

Large-capacity DNA vectors based on rolling circle amplification with multivalent aptamers delivery copper sulfide for the synergistic treatment of Cancer through chemo/Photothermal/Chemodynamic therapy in vitro

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-17 DOI: 10.1016/j.jinorgbio.2025.112831

Huan Du, Fang Wang, Ruyan Zhang, Yan Ma, Xiaobing Huo, Gan Ning, Xiufeng Wang, Ting Zhou, Guodong Zhang, Zhiqing Zhang

Developing multifunctional nanomedicines represents a frontier. We have engineered a high-capacity DNA vector basing rolling circle amplification for the delivery of copper sulfide nanoparticles (CuS NPs) and doxorubicin (DOX), coupled with multivalent aptamers (MA) that precisely target tumors, culminating in a multifunctional nanoplatform (RMAL₁Cu@DOX), which combines the chemotherapy (CT)/photothermal therapy (PTT)/chemodynamic therapy (CDT). The vector (RMAL₁) boasts exceptional biocompatibility and incorporates multiple copy units, enabling the precise loading of numerous CuS NPs, forming RMAL₁Cu which possesses a robust photothermal effect and superior Fenton-like catalytic activity, heralding a project of minimally invasive dual-mode (PTT/CDT) therapy. Furthermore, the abundance of G-C of RMAL₁ enabled effective DOX encapsulation through π-π interactions to construct RMAL₁Cu@DOX. The MA integrated into RMAL₁Cu@DOX is pivotal in enhancing the targeting of tumors and in preventing non-specific release of CuS and DOX, enabling an integrated CT/PTT/CDT. Data indicate that 1 nM of RMAL₁Cu could load 270 nM of DOX with an impressive loading capacity of 77 %, and modification with MA, its tumor-targeting ability was amplified by 51-fold and significantly bolstered in vitro imaging outcomes, and the synergistic killing of B16 was as 67.3 %. This innovative nanoplatform offers a comprehensive and holistic strategy for the treatment of malignant tumors.

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引用次数: 0

Binding a C12-appended rhenium-(Bispyridine) carbonyl complex to β-Lactoglobulin: Effects of pH & cysteine modification on calyx affinity 将 C12 添加的铼-（双吡啶）羰基复合物与 β-乳球蛋白结合：pH 值和半胱氨酸修饰对花萼亲和力的影响。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-13 DOI: 10.1016/j.jinorgbio.2025.112828

Emily E. Stumbo , Sean T. Goralski , Phillip R. Leclair, Spencer Kerns, Michael J. Rose

Due to its commercial availability and well-defined structure, the interaction between bovine protein β-lactoglobulin (βLG) and a wide variety of non-native ligands — including transition metal complexes — has been explored, but its application as an artificial metalloenzyme scaffold is limited. This protein is hypothesized to transport fatty acids and other nutrients during juvenile development, and it binds hydrophobic ligands inside a binding pocket constructed upon an 8-stranded β-barrel, called the ‘calyx’. Herein, we compare the binding behavior of two rhenium(anthracene-bispyridine) (‘Anth-py₂’) tricarbonyl complexes, one with a 12‑carbon chain appended to the ligand scaffold (‘^C12Anth-py₂’) to βLG. We investigate (i) how calyx-binding specificity is affected by pH (which controls βLG structure at the entrance to the calyx) and (ii) modification of a free cysteine residue located in a putative second binding site of βLG (SMe-βLG). The binding affinities of [Re(^C12Anth-py₂)(CO)₃(solv)]⁺ (ReC₁₂) and [Re(Anth-py₂)(CO)₃(solv)]⁺ (ReCH) for βLG at pH 7.3 were similar at 36 ± 2 μM and 43 ± 1 μM, respectively. The K_D of ReC₁₂ decreased by ∼13 μM at pH 6.1 due to a well-known conformational change (Tanford transition) at the entrance to the calyx; the K_D value was not significantly affected by Cys121 modification, indicating β-barrel calyx binding specificity. In contrast, ReCH experienced a decrease in K_D in response to blocking the second binding (SMe-βLG), but was also unaffected by pH. The results show an increase in binding affinity and specificity as a result of targeted ligand design and utilization of native protein characteristics. The findings will inform and improve the design of future βLG-derived ArMs.

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引用次数: 0

Nitrite binding to myoglobin and hemoglobin: Reactivity and structural aspects

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-11 DOI: 10.1016/j.jinorgbio.2025.112829

Paolo Ascenzi , Giovanna De Simone , Gabriele Antonio Zingale , Massimo Coletta

Nitrite (NO₂⁻) interacts with myoglobin (Mb) and hemoglobin (Hb) behaving as a ligand of both the ferrous (i.e., Mb(II) and Hb(II)) and ferric (i.e., Mb(III) and Hb(III)) forms. However, while the binding to the Fe(III) species corresponds to the formation of a stable complex (i.e., Mb(III)-NO₂⁻ and Hb(III)-NO₂⁻), in the case of the ferrous forms the reaction proceeds with a nitrite reductase redox process, leading to the oxidation of the heme-protein with the reduction of NO₂⁻ to NO. This event is of the utmost importance for the rapid production of NO in vivo in the blood stream and in striated muscles, being crucial for the regulation of the blood flow, and thus for O₂ supply to poorly oxygenated tissues, such as the eye's retina. Further, NO₂⁻ interacts with Mb(II)-O₂ and Hb(II)-O₂, inducing their oxidation with a complex mechanism, which has been only partially elucidated. Mb and Hb form the complex with NO₂⁻ through the O-nitrito binding mode (i.e., Fe-ONO⁻), which is regulated by residues paving the heme distal side; thus, in a site-directed mutant, where HisE7 is substituted by Val, the interaction occurs in the N-nitro binding mode (i.e., Fe-N(O)O⁻), like in most other heme-proteins. The structure-function relationships of the interaction of NO₂⁻ with both ferric and ferrous forms of Mb and Hb are discussed here.

{"title":"Nitrite binding to myoglobin and hemoglobin: Reactivity and structural aspects","authors":"Paolo Ascenzi , Giovanna De Simone , Gabriele Antonio Zingale , Massimo Coletta","doi":"10.1016/j.jinorgbio.2025.112829","DOIUrl":"10.1016/j.jinorgbio.2025.112829","url":null,"abstract":"<div><div>Nitrite (NO2−) interacts with myoglobin (Mb) and hemoglobin (Hb) behaving as a ligand of both the ferrous (i.e., Mb(II) and Hb(II)) and ferric (i.e., Mb(III) and Hb(III)) forms. However, while the binding to the Fe(III) species corresponds to the formation of a stable complex (i.e., Mb(III)-NO2− and Hb(III)-NO2−), in the case of the ferrous forms the reaction proceeds with a nitrite reductase redox process, leading to the oxidation of the heme-protein with the reduction of NO2− to NO. This event is of the utmost importance for the rapid production of NO in vivo in the blood stream and in striated muscles, being crucial for the regulation of the blood flow, and thus for O2 supply to poorly oxygenated tissues, such as the eye's retina. Further, NO2− interacts with Mb(II)-O2 and Hb(II)-O2, inducing their oxidation with a complex mechanism, which has been only partially elucidated. Mb and Hb form the complex with NO2− through the O-nitrito binding mode (i.e., Fe-ONO−), which is regulated by residues paving the heme distal side; thus, in a site-directed mutant, where HisE7 is substituted by Val, the interaction occurs in the N-nitro binding mode (i.e., Fe-N(O)O−), like in most other heme-proteins. The structure-function relationships of the interaction of NO2− with both ferric and ferrous forms of Mb and Hb are discussed here.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"265 ","pages":"Article 112829"},"PeriodicalIF":3.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035710","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}

引用次数: 0

Palladium(II) complexes containing andrographolide appended N,O heterocyclic chelators: Investigation of anti-oxidant, anti-cancer and apoptotic activities

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-11 DOI: 10.1016/j.jinorgbio.2025.112830

Priya Prasad , S. Parveen , Abdullah A. Alarfaj , Abdurahman Hajinur Hirad , M. Mohamed Subarkhan , S. Dhanapal , G. Kalaiarasi

A series of new Pd(II) complexes were synthesized from the reaction of andrographolide appended hydrazide derivatives with potassium tetrachloropalladate K₂[PdCl₄]. The formation of the complexes was confirmed through structural assessments conducted using various spectroscopic techniques. From the spectral studies we confirmed that the ligands coordinated to Pd(II) ion via amine nitrogen and enone oxygen. The complexes were assessed for their antioxidant properties, demonstrating significant radical scavenging activity with a series of free radicals such as 1,1-diphenyl-2-picrylhydrazyl (DPPH^•), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid diammonium salt (ABTS^•+), Super oxide (O²⁻) and Nitric oxide (NO^•) radicals compared with standard antioxidants. Moreover, in vitro antiproliferative investigations conducted on A549 (human lung cancer) and HeLa (human cervical cancer) cell lines revealed significant cytotoxicity of the complexes, with lower IC₅₀ values compared to the standard metallo-drug cisplatin. Morphological alterations observed in HeLa and A549 cells when treated with IC₅₀ concentrations of the complexes, as examined through Acridine Orange-Ethidium Bromide (AO-EB) and 4′,6-diamidino-2-phenylindole (DAPI) staining techniques, indicated cell death via apoptosis. Biological studies indicated that AGC-Pd exhibited superior activity among others, further the percentages of the apoptotic and necrotic cells were determined by flow cytometric technique.

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引用次数: 0

Accessing iridium Cp* as a cofactor for artificial metalloenzymes 获得铱Cp*作为人工金属酶的辅助因子。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2025-01-03 DOI: 10.1016/j.jinorgbio.2024.112820

Oskar James Klein, Armando Albert-Flores, Matthew G. Wheeler, Katherine Rojales, Andrew D. Bond, Sally R. Boss, Paul D. Barker

By introducing new-to-nature transformations, artificial metalloenzymes hold great potential for expanding the biosynthetic toolbox. The chemistry of an active cofactor in these enzymes is highly dependent on how the holoprotein is assembled, potentially limiting the choice of organometallic complexes amenable to incorporation and ability of the protein structure to influence the metal centre. We have previously reported a method utilising ligand exchange as a means to introduce ruthenium-arene fragments into a four-helix bundle protein. In this work we expand the scope of this method to incorporate an iridium pentamethylcyclopentadienyl fragment into a four-helix bundle, yielding an artificial metalloenzyme with improved transfer hydrogenation properties, highlighting that understanding ligand exchange reactions is important for speciation control.

通过引入新的自然转化，人工金属酶具有扩大生物合成工具箱的巨大潜力。这些酶中活性辅助因子的化学性质高度依赖于全蛋白的组装方式，这可能限制了适合结合的有机金属配合物的选择以及蛋白质结构影响金属中心的能力。我们以前曾报道过一种利用配体交换将钌-芳烃片段引入四螺旋束蛋白的方法。在这项工作中，我们扩展了该方法的范围，将五甲基环戊二烯铱片段纳入四螺旋束，产生具有改善转移氢化性能的人工金属酶，强调了解配体交换反应对物种形成控制的重要性。

引用次数: 0

Ruthenium(II)-mercapto complexes induce cell damage via apoptosis pathway on ovarian cancer cells 钌(II)-巯基复合物通过凋亡途径诱导卵巢癌细胞损伤。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2024-12-30 DOI: 10.1016/j.jinorgbio.2024.112819

Marcos V. Palmeira-Mello , Tamara Teixeira , Matheus Reis Santos de Melo , Heloiza Diniz Nicolella , Jocely L. Dutra , Marcia R. Cominetti , Fillipe Vieira Rocha , Denise Crispim Tavares , Alzir A. Batista

Ovarian cancer represents a leading cause of cancer-related deaths in women worldwide. Chemotherapeutic agents are usually employed to treat the patients, and Ruthenium(II)-based compounds have been investigated as possible substitutes for platinum drugs. In this work, we studied three different Ru(II)-phosphine-mercapto complexes (1–3) as potential cytotoxic agents against A2780 and A2780-cisR ovarian cancer cells. A time-dependent cytotoxicity was observed for 2, which also exhibited better selectivity than cisplatin control. A similar cytotoxic behavior was observed on 3D tumor spheroids. Although no changes were observed in cell cycle distribution, compound 2 affected the mitochondrial membrane potential on A2780 cells, and caused cell death via apoptotic pathway, which was confirmed by flow cytometry assay. Western blotting experiments revealed that 2 affected the expression of p53, PCNA, γH2AX and cleaved caspase-3, making it a promising anticancer agent for ovarian cancer.

卵巢癌是全世界妇女癌症相关死亡的主要原因。化疗药物通常用于治疗患者，钌（II）基化合物已被研究作为铂类药物的可能替代品。在这项工作中，我们研究了三种不同的Ru(II)-膦-巯基络合物（1-3）作为抗A2780和A2780- cisr卵巢癌细胞的潜在细胞毒性药物。观察到2的时间依赖性细胞毒性，也表现出比顺铂对照组更好的选择性。在三维肿瘤球体上观察到类似的细胞毒性行为。虽然没有观察到细胞周期分布的变化，但化合物2影响了A2780细胞的线粒体膜电位，并通过凋亡途径引起细胞死亡，流式细胞术实验证实了这一点。Western blotting实验显示，2能影响p53、PCNA、γ - h2ax和cleaved caspase-3的表达，是一种很有前景的卵巢癌抗癌药物。

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引用次数: 0

Corrigendum to “Spectrofluorimetric analysis of the binding of a target molecule to serum albumin: tricky aspects and tips” [Journal of Inorganic Biochemistry 216 (2021) 111305] “靶分子与血清白蛋白结合的荧光光谱分析：棘手的方面和提示”[无机生物化学杂志216(2021)111305]的勘误表。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2024-12-28 DOI: 10.1016/j.jinorgbio.2024.112817

Francesca Macii , Tarita Biver

引用次数: 0

Unsymmetrical salen-based oxido VIV: Synthesis, characterization, biomolecular interactions, and anticancer activity 不对称salen基氧化物VIV：合成、表征、生物分子相互作用和抗癌活性。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2024-12-25 DOI: 10.1016/j.jinorgbio.2024.112818

Deepika Mohapatra , Pratikshya Das Pattanayak , Souvik Chatterjee , Werner Kaminsky , Takahiro Sasamori , Takashi Nakamura , Rupam Dinda

Three stable oxidovanadium(IV) [V^IVOL^1–3] complexes (1–3) were synthesized through the incorporation of unsymmetrical salen ligands (H₂L¹⁻³). All the ligands are synthesized, and their vanadium compounds were thoroughly characterized by CHNS analysis, various spectroscopy methods (IR, UV–Vis, NMR spectroscopy), and HR–ESI–MS. The structures of 1–3 were validated through the single-crystal X-ray analysis. UV–Vis and HR–ESI–MS were used to determine the solution stability of the complexes in the aqueous phase, revealing their stability in aqueous/biological medium. Various spectroscopy techniques were used to study the DNA/BSA binding abilities, and the results indicate that 1–3 shows effective biomolecular interactions. The partition coefficient result indicates that 1–3 are highly hydrophobic and may easily permeate the cells. Finally, the in vitro anticancer properties of 1–3 were determined with two cancerous (HT-29 and A549), and the NIH-3T3 normal cell lines. Among the series, 3 is the most cytotoxic, with IC₅₀ values of 6.2 ± 0.2 and 5.3 ± 0.4 μM against HT-29 and A549 cell lines respectively. Moreover, the apoptotic cell death mechanism of 1–3 was assessed through DAPI, AO/EB, and double staining apoptosis experiments.

通过不对称salen配体（H2L1-3）的掺入，合成了三个稳定的氧化钒（IV） [VIVOL1-3]配合物（1-3）。合成了所有配体，并通过CHNS分析、各种光谱方法（IR、UV-Vis、NMR）和HR-ESI-MS对其钒化合物进行了全面表征。其中1-3的结构通过单晶x射线分析得到验证。采用UV-Vis和HR-ESI-MS测定配合物在水相中的稳定性，揭示其在水/生物介质中的稳定性。利用各种光谱技术研究了DNA/BSA的结合能力，结果表明1-3表现出有效的生物分子相互作用。分配系数结果表明，1-3是高度疏水性的，很容易渗透细胞。最后，用两种癌变细胞系HT-29和A549，以及NIH-3T3正常细胞系，测定1-3的体外抗癌特性。其中，3对HT-29和A549细胞株的IC50值分别为6.2±0.2和5.3±0.4 μM，细胞毒性最强。并通过DAPI、AO/EB、双染色凋亡实验对1-3的凋亡细胞死亡机制进行评估。

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引用次数: 0

Molecular basis of H2O2/O2.−/.OH discrimination during electrochemical activation of DyP peroxidases: The critical role of the distal residues H2O2/O2.-/的分子基础。在DyP过氧化物酶的电化学活化过程中的OH辨别：远端残基的关键作用。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2024-12-22 DOI: 10.1016/j.jinorgbio.2024.112816

Magalí F. Scocozza , Ulises A. Zitare , Pablo Cancian , María A. Castro , Lígia O. Martins , Daniel H. Murgida

Here, we show that the replacement of the distal residues Asp and/or Arg of the DyP peroxidases from Bacillus subtilis and Pseudomonas putida results in functional enzymes, albeit with spectroscopically perturbed active sites. All the enzymes can be activated either by the addition of exogenous H₂O₂ or by in situ electrochemical generation of the reactive oxygen species (ROS) ^•OH, O₂^•- and H₂O₂. The latter method leads to broader and upshifted pH-activity profiles. Both WT enzymes exhibit a differential predominance of ROS involved in their electrochemical activation, which follows the order ^•OH > O₂^•- > H₂O₂ for BsDyP and O₂^•- > H₂O₂ > ^•OH for PpDyP. This ROS selectivity is preserved in mutants with unperturbed sites but is blurred out for distorted sites. The underlying molecular basis of the selectivity mechanisms is analysed through molecular dynamics simulations, which reveal distorted hydrogen bonding networks and higher throughput of the access tunnels in the variants exhibiting no selectivity. The electrochemical activation method provides superior performance for protein variants with a high prevalence of the alternative ^•OH and O₂^•- species. These results constitute a promising advance towards engineering DyPs for electrocatalytic applications.

在这里，我们证明了从枯草芽孢杆菌和恶臭假单胞菌中替换DyP过氧化物酶的远端残基Asp和/或Arg会产生功能性酶，尽管具有光谱扰动的活性位点。所有的酶都可以通过添加外源H2O2或通过原位电化学生成活性氧（ROS）•OH、O2•-和H2O2来激活。后一种方法可以得到更宽的ph -活度曲线。两种WT酶在其电化学激活过程中都表现出不同的ROS优势，其顺序为：•OH > O2•- > H2O2 （BsDyP）和O2•- > H2O2 >•OH （PpDyP）。这种ROS选择性在具有未受干扰位点的突变体中保留，但对于扭曲位点则模糊了。通过分子动力学模拟分析了选择性机制的分子基础，揭示了无选择性的变体中氢键网络的扭曲和通道的高通量。电化学活化方法对具有高选择性•OH和O2•-的蛋白质变体提供了优越的性能。这些结果构成了电催化应用的工程DyPs的有希望的进展。

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引用次数: 0

Designing mimosine-containing peptides as efficient metal chelators: Insights from molecular dynamics and quantum calculations 设计含氨基茉莉肽作为有效的金属螯合剂：从分子动力学和量子计算的见解。

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry

Pub Date : 2024-12-20 DOI: 10.1016/j.jinorgbio.2024.112807

D. Silva-Brea , J. Aduriz-Arrizabalaga , D. De Sancho , X. Lopez

Mimosine, a non-essential amino acid derived from plants, has a strong affinity for binding divalent and trivalent metal cations, including Zn²⁺, Ni²⁺, Fe^2+/3+, and Al³⁺. This ability endows mimosine with significant antimicrobial and anti-cancer properties, making it a promising candidate for therapeutic applications. Previous research has demonstrated the effectiveness of mimosine-containing peptides as metal chelators, offering a safer alternative to conventional chelation agents. However, optimizing the design of these peptides necessitates a thorough understanding of their conformational ensembles in both free and metal-bound states. Here, we perform an in-depth analysis of mimosine-containing peptides using long-time MD simulations and quantum calculations to identify key factors critical for peptide design. Our results show that these peptides can achieve metal-binding affinities comparable to established aluminum chelators like deferiprone and citrate. Additionally, we underscore the crucial role of the peptide backbone in reducing the entropic penalty associated with metal binding. We propose strategies to modulate this entropic penalty—a challenging thermodynamic property to evaluate but essential in complexes between short peptides and metals—by incorporating proline residues and optimizing sequence length. These approaches offer promising pathways for developing efficient peptide chelators.

氨基草胺是一种来源于植物的非必需氨基酸，对二价和三价金属阳离子具有很强的亲和力，包括Zn2+、Ni2+、Fe2+/3+和Al3+。这种能力赋予了氨基糖显著的抗菌和抗癌特性，使其成为治疗应用的有希望的候选者。先前的研究已经证明了含氨基茉莉肽作为金属螯合剂的有效性，提供了一种比传统螯合剂更安全的替代品。然而，优化这些肽的设计需要彻底了解它们在自由和金属结合状态下的构象组合。在这里，我们使用长时间的MD模拟和量子计算来深入分析含氨基酪氨酸的肽，以确定肽设计的关键因素。我们的研究结果表明，这些肽可以达到金属结合亲和力，可与已建立的铝螯合剂，如去铁氨酸和柠檬酸盐相媲美。此外，我们强调了肽主链在减少与金属结合相关的熵惩罚方面的关键作用。我们提出了一些策略来调节这种熵罚——一种具有挑战性的热力学性质来评估，但在短肽和金属之间的复合物中是必不可少的——通过结合脯氨酸残基和优化序列长度。这些方法为开发高效的肽螯合剂提供了有希望的途径。

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引用次数: 0