Journal of Inorganic Biochemistry最新文献

{"title":"Tri-aryl antimony(V) hydroximato and hydroxamato complexes: Combining lipophilic Sb(III/V) and hydroxamic acids in combating Leishmania","authors":"Charles R.M. Soukup,&nbsp;Rebekah N. Duffin,&nbsp;Kirralee J. Burke,&nbsp;Philip C. Andrews","doi":"10.1016/j.jinorgbio.2024.112674","DOIUrl":"10.1016/j.jinorgbio.2024.112674","url":null,"abstract":"<div><p>Six novel tri-aryl antimony(V) hydroximato complexes (<strong>3–8</strong>) with composition [SbAr₃(O₂NCR)] (<strong>3</strong>: Ar = Ph, R = <em>o</em>-(OH)Ph, <strong>4</strong>: Ar = Ph, R = Me, <strong>5</strong>: Ar = Ph, R = Ph; <strong>6</strong>: Ar = Mes, R = Me, <strong>7</strong>: Ar = Mes, R = Ph, <strong>8</strong>: Ar = Mes, R = <em>o</em>-(OH)Ph (where Ph = phenyl, Me = methyl, Mes = mesityl)), were synthesised and evaluated for anti-parasitic activity towards <em>Leishmania major</em> (<em>L. major</em>) promastigotes and amastigotes. Complexes of the form [SbAr₃(O₂NCR)], with the dianionic hydroximato ligand binding <em>O,O′</em>-bidentate to the Sb(V) centre, exist in the solid-state for the mesityl-derived complexes. In contrast, the phenyl-ligated Sb(V) complexes crystallise as the hexacoordinate, hydroxamato species [SbPh₃(O₂NHC(OH))], with the OH ligand derived from entrained H₂O in the crystallisation solvent. It is found that both the aryl and hydroximato ligands are found to influence the bioactivity of the Sb(V) complexes. Complexes <strong>3–8</strong> exhibited varied anti-promastigote activity with IC₅₀ values ranging from 1.53 μM for <strong>6</strong> to 36.0 μM for <strong>3</strong>, also reflected in varied anti-amastigote activity with a percentage infection range of 5.50% for <strong>6</strong> to 29.00% for <strong>3</strong> at a concentration of 10 μM. The complexes were relatively non-toxic to human fibroblasts with an IC₅₀ value range of 59.3 μM (<strong>7</strong>) to ≥100 μM (<strong>3–6</strong>, <strong>8</strong>), and exhibited varied toxicity towards J774.1 A macrophages (IC₅₀: 3.97 (<strong>6</strong>) to ≥100 (<strong>8</strong>) μM). All complexes showed enhanced activity compared to the parent hydroxamic acids.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"260 ","pages":"Article 112674"},"PeriodicalIF":3.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424001983/pdfft?md5=95fa2fb1ccaca4c5a1d6ff65e05284e1&pid=1-s2.0-S0162013424001983-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851112","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":"Ga complexes of 8-hydroxyquinoline-2-carboxylic acid: Chemical speciation and biological activity","authors":"Izabela Ryza ,&nbsp;Claudia Granata ,&nbsp;Nadia Ribeiro ,&nbsp;Edyta Nalewajko-Sieliwoniuk ,&nbsp;Andreas Kießling ,&nbsp;Marta Hryniewicka ,&nbsp;Winfried Plass ,&nbsp;Beata Godlewska-Żyłkiewicz ,&nbsp;Sandra Cabo Verde ,&nbsp;Demetrio Milea ,&nbsp;Sofia Gama","doi":"10.1016/j.jinorgbio.2024.112670","DOIUrl":"10.1016/j.jinorgbio.2024.112670","url":null,"abstract":"<div><p>The binding ability of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) towards Ga³⁺ has been investigated by ISE<img>H⁺ (Ion Selective Electrode, glass electrode) potentiometric and UV/Vis spectrophotometric titrations in KCl_(aq) at <em>I</em> = 0.2 mol dm⁻³ and at <em>T</em> = 298.15 K. Further experiments were also performed adopting both the metal (with Fe³⁺ as competing cation) and ligand-competition approaches (with EDTA as competing ligand). Results gave evidence of the formation of the [Ga(8-HQA)]⁺, [Ga(8-HQA)(OH)], [Ga(8-HQA)(OH)₂]⁻ and [Ga(8-HQA)₂]⁻ species, the latter being so far the most stable, as also confirmed by ESI-MS analysis. Experiments were also designed to determine the stability constants of the [Ga(EDTA)]⁻ and [Ga(EDTA)(OH)]²⁻ in the above conditions. Due to the relevance of Ga³⁺ hydrolysis in aqueous systems, literature data on this topic were collected and critically analyzed, providing equations for the calculation of mononuclear Ga³⁺ hydrolysis constants at <em>T</em> = 298.15 K, in different ionic media, in the ionic strength range 0 &lt; <em>I</em> / mol dm⁻³ ≤ 1.0. The synthesis and characterization (by ElectroSpray Ionization – Mass Spectrometry (ESI-MS), Attenuated Total Reflectance - Fourier-Transform Infrared Spectroscopy (ATR-FTIR) and ThermoGravimetric Analysis (TGA)) of Ga³⁺/8-HQA complexes were also performed, identifying [Ga(8-HQA)₂]⁻ as the main isolated species, even in the solid state. Finally, the potential effects of 8-HQA and Ga³⁺/8-HQA complex towards human microbiota exposed to ionizing radiation were evaluated (namely <em>Actinomyces viscosus</em>, <em>Streptococcus mutans</em>, <em>Streptococcus sobrinus</em>, <em>Pseudomonas putida</em>, <em>Pseudomonas fluorescens</em> and <em>Escherichia coli</em>), as well as their anti-proliferative and anti-inflammatory properties. A radioprotective effect of Ga³⁺/8-HQA complex was observed on <em>Actinomyces viscosus</em>, while showing a potential radiosensitizing effect against <em>Streptococcus mutans</em> and <em>Streptococcus sobrinus</em>. No cytotoxicity on RAW264.7 murine macrophage cells was observed, neither for the free ligand or Ga³⁺/8-HQA complex. Nevertheless, Ga³⁺/8-HQA complex highlighted potential anti-inflammatory properties.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"260 ","pages":"Article 112670"},"PeriodicalIF":3.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0162013424001946/pdfft?md5=8071b26e3edf40d588f6eeed3f706ad6&pid=1-s2.0-S0162013424001946-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786943","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":"Resonance Raman spectral analysis of the heme site structure of cytochrome c oxidase with its positive regulator CHCHD2","authors":"Sachiko Yanagisawa ,&nbsp;Takuto Kamei ,&nbsp;Atsuhiro Shimada ,&nbsp;Stephanie Gladyck ,&nbsp;Siddhesh Aras ,&nbsp;Maik Hüttemann ,&nbsp;Lawrence I. Grossman ,&nbsp;Minoru Kubo","doi":"10.1016/j.jinorgbio.2024.112673","DOIUrl":"10.1016/j.jinorgbio.2024.112673","url":null,"abstract":"<div><p>Cytochrome <em>c</em> oxidase (CcO) reduces O₂, pumps protons in the mitochondrial respiratory chain, and is essential for oxygen consumption in the cell. The coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2; also known as mitochondrial nuclear retrograde regulator 1 [MNRR1], Parkinson's disease 22 [PARK22] and aging-associated gene 10 protein [AAG10]) is a protein that binds to CcO from the intermembrane space and positively regulates the activity of CcO. Despite the importance of CHCHD2 in mitochondrial function, the mechanism of action of CHCHD2 and structural information regarding its binding to CcO remain unknown. Here, we utilized visible resonance Raman spectroscopy to investigate the structural changes around the hemes in CcO in the reduced and CO-bound states upon CHCHD2 binding. We found that CHCHD2 has a significant impact on the structure of CcO in the reduced state. Mapping of the heme peripheries that result in Raman spectral changes in the structure of CcO highlighted helices IX and X near the hemes as sites where CHCHD2 takes action. Part of helix IX is exposed in the intermembrane space, whereas helix X, located between both hemes, may play a key role in proton uptake to a proton-loading site in the reduced state for proton pumping. Taken together, our results suggested that CHCHD2 binds near helix IX and induces a structural change in helix X, accelerating proton uptake.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"260 ","pages":"Article 112673"},"PeriodicalIF":3.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141853892","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":"Synthesis, physicochemical and pharmacological characterizations of a tetra-[methylimidazolium] dihydrogen decavanadate, inhibiting the IGR39 human melanoma cells development","authors":"Taissir Aissa ,&nbsp;Dorra Aissaoui-Zid ,&nbsp;Wassim Moslah ,&nbsp;Oussema Khamessi ,&nbsp;Regaya Ksiksi ,&nbsp;Maike Oltermann ,&nbsp;Michael Ruck ,&nbsp;Mohamed Faouzi Zid ,&nbsp;Najet Srairi-Abid","doi":"10.1016/j.jinorgbio.2024.112672","DOIUrl":"10.1016/j.jinorgbio.2024.112672","url":null,"abstract":"<div><p>Melanoma is a skin cancer that arises from melanocytes and can spread quickly to the other organs of the body, if not treated early. Generally, melanoma shows an inherent resistance to conventional therapies. In this regard, new potential drugs are being developed as possible treatments for melanoma. In this paper, we report the synthesis of a new decavanadate compound with organic molecules for a potential therapeutic application. The tetra-[methylimidazolium] dihydrogen decavanadate(V) salt (C₄H₇N₂)₄[H₂V₁₀O₂₈] is characterized by single-crystal X-ray diffraction, by FT-IR, UV–Vis and ⁵¹V NMR spectroscopy, as well as by thermal analysis (TGA and DSC). The compound crystallizes in the monoclinic centrosymmetric space group <em>P</em>2₁/<em>c</em>. Its formula unit consists of one dihydrogen decavanadate anion [H₂V₁₀O₂₈]⁴⁻ and four organic 4-methylimidazolium cations (C₄H₇N₂)⁺. Important intermolecular interactions are N-H···O and O-H···O hydrogen bonds and π-π stacking interactions between the organic cations, revealed by analysis of the Hirshfeld surface and its two-dimensional fingerprint plots. Interestingly, this compound inhibits the viability of IGR39 cells with IC₅₀ values of 14.65 μM and 4 μM after 24 h and 72 h of treatment, respectively. The analysis of its effect by flow cytometry using an Annexin V-FITC/IP cell labeling, showed that (C₄H₇N₂)₄H₂V₁₀O₂₈ compound induced IGR39 cell apoptosis and necrosis. Molecular docking studies performed against TNFR1 and GPR40, as putative targets, suggest that the (C₄H₇N₂)₄[H₂V₁₀O₂₈] compound may act as inhibitor of these proteins, known to be overexpressed in melanoma cells. Therefore, we could consider it as a new potential metallodrug against melanoma.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"260 ","pages":"Article 112672"},"PeriodicalIF":3.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141853588","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":"Impressive promiscuous biomimetic models of ascorbate, amine, and catechol oxidases","authors":"Balasubramaniam Selvakumaran,&nbsp;Mariappan Murali,&nbsp;Selvaraj Shanmugavadivel,&nbsp;Venkatesan Sindhuja,&nbsp;Velusamy Sathya","doi":"10.1016/j.jinorgbio.2024.112671","DOIUrl":"10.1016/j.jinorgbio.2024.112671","url":null,"abstract":"<div><p>Copper metalloenzymes ascorbate oxidase (AOase), amine oxidase (AmOase), and catechol oxidase (COase) possess copper(II) sites of coordination, which are trimeric, homodimeric, and dimeric, respectively. Two newly mononuclear copper(II) complexes, namely, [Cu(L)(bpy)](ClO₄) (<strong>1</strong>) and [Cu(L)(phen)](ClO₄) (<strong>2</strong>) where HL = Schiff base, have been synthesized. UV–visible, EPR and single-crystal X-ray diffraction examinations were used to validate the geometry in solution and solid state. For complex <strong>1</strong>, the metal exhibits a coordination sphere between square pyramidal and trigonal bipyramidal geometry (τ, 0.49). A positive Cu^II/^I redox potential indicates a stable switching between Cu^II and Cu^I redox states. Despite the monomeric origin, both homogeneous catalysts (<strong>1 or 2)</strong> in MeOH were found to favor three distinct chemical transformations, namely, ascorbic acid (H₂A) to dehydroascorbic acid (DA), benzylamine (Ph-CH₂-NH₂) to benzaldehyde (Ph-CHO), and 3,5-di-<em>tert</em>-butylcatechol (3,5-DTBC) to 3,5-di-<em>tert</em>-butylquinone (3,5-DTBQ) [<em>k</em>_cat: AOase, 9.6 (<strong>1</strong>) or 2.0 × 10⁶ h⁻¹(<strong>2</strong>); AmOase, 13.4 (<strong>1</strong>) or 9.4 × 10⁶ h⁻¹ (<strong>2</strong>); COase, 2.0 (<strong>1</strong>) or 1.9 × 10³ h⁻¹ (<strong>2</strong>)]. They exhibit higher levels of AOase activity as indicated by their <em>k</em>_cat values compared to the AOase enzyme. The <em>k</em>_cat values for COase activity in buffer solution [5.93 (<strong>1</strong>) or 2.95 × 10⁵ h⁻¹ (<strong>2</strong>)] are one order lower than those of the enzymes. This is because of the labile nature of the coordinated donor, the flexibility of the ligand, the simplicity of the catalyst-substrate interaction, and the positive Cu^II/^I redox potential. Interestingly, more efficient catalysis is promoted by <strong>1</strong> and <strong>2</strong> concerning that of other mono- and dicopper(II) complexes.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"259 ","pages":"Article 112671"},"PeriodicalIF":3.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764701","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":"Enzymatic CO2 reduction catalyzed by natural and artificial Metalloenzymes","authors":"Yunling Deng,&nbsp;Jing-Xiang Wang,&nbsp;Barshali Ghosh,&nbsp;Yi Lu","doi":"10.1016/j.jinorgbio.2024.112669","DOIUrl":"10.1016/j.jinorgbio.2024.112669","url":null,"abstract":"<div><p>The continuously increasing level of atmospheric CO₂ in the atmosphere has led to global warming. Converting CO₂ into other carbon compounds could mitigate its atmospheric levels and produce valuable products, as CO₂ also serves as a plentiful and inexpensive carbon feedstock. However, the inert nature of CO₂ poses a major challenge for its reduction. To meet the challenge, nature has evolved metalloenzymes using transition metal ions like Fe, Ni, Mo, and W, as well as electron-transfer partners for their functions. Mimicking these enzymes, artificial metalloenzymes (ArMs) have been designed using alternative protein scaffolds and various metallocofactors like Ni, Co, Re, Rh, and Fe<img>S clusters. Both the catalytic efficiency and the scope of CO₂-reduction product of these ArMs have been improved over the past decade. This review first focuses on the natural metalloenzymes that directly reduce CO₂ by discussing their structures and active sites, as well as the proposed reaction mechanisms. It then introduces the common strategies for electrochemical, photochemical, or photoelectrochemical utilization of these native enzymes for CO₂ reduction and highlights the most recent advancements from the past five years. We also summarize principles of protein design for bio-inspired ArMs, comparing them with native enzymatic systems and outlining challenges and opportunities in enzymatic CO₂ reduction.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"259 ","pages":"Article 112669"},"PeriodicalIF":3.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764700","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":"One His, two His…the emerging roles of histidine in cellular nickel trafficking","authors":"Peter T. Chivers ,&nbsp;Priyanka Basak ,&nbsp;Michael J. Maroney","doi":"10.1016/j.jinorgbio.2024.112668","DOIUrl":"10.1016/j.jinorgbio.2024.112668","url":null,"abstract":"<div><p>Biological environments present a complex array of metal-binding ligands. Metal-binding proteins have been the overwhelming focus of study because of their important and well-defined biological roles. Consequently, the presence of functional low molecular weight (LMW) metal-ligand complexes has been overlooked in terms of their roles in metallobiochemistry, particularly within cells. Recent studies in microbial systems have illuminated the different roles of L-histidine in nickel uptake, gene expression, and metalloenzyme maturation. In this focused critical review, these roles are surveyed in the context of the coordination chemistry of Ni(II) ions and the amino acid histidine, and the physico-chemical properties of nickel complexes of histidine. These complexes are fundamentally important to cellular metal homeostasis and further work is needed to fully define their contributions.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"259 ","pages":"Article 112668"},"PeriodicalIF":3.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756374","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":"A flexible linker of 8-amino acids between the membrane binding segment and the FMN domain of cytochrome P450 reductase is necessary for optimal activity","authors":"Freeborn Rwere ,&nbsp;Naw May P. Cartee ,&nbsp;Yuting Yang ,&nbsp;Lucy Waskell","doi":"10.1016/j.jinorgbio.2024.112667","DOIUrl":"10.1016/j.jinorgbio.2024.112667","url":null,"abstract":"<div><p>The diflavin NADPH-cytochrome P450 reductase (CYPOR) plays a critical role in human cytochrome P450 (CYP) activity by sequentially delivering two electrons from NADPH to CYP enzymes during catalysis. Although electron transfer to forty-eight human CYP enzymes by the FMN hydroquinone of CYPOR is well-known, the role of the linker between the NH₂-terminus membrane-binding domain (MBD) and FMN domain in supporting the activity of P450 enzymes remains poorly understood. Here we demonstrate that a linker with at least eight residues is required to form a functional CYPOR-CYP2B4 complex. The linker has been shortened in two amino-acid increments from Phe44 to Ile57 using site directed mutagenesis. The ability of the deletion mutants to support cytochrome P450 2B4 (CYP2B4) catalysis and reduce ferric CYP2B4 was determined using an in vitro assay and stopped-flow spectrophotometry. Steady-state enzyme kinetics showed that shortening the linker by 8–14 amino acids inhibited (63–99%) the ability of CYPOR to support CYP2B4 activity and significantly increased the K_m of CYPOR for CYP2B4. In addition, the reductase mutants decreased the rate of reduction of ferric CYP2B4 (46–95%) compared to wildtype when the linker was shortened by 8–14 residues. These results indicate that a linker with a minimum length of eight residues is necessary to enable the FMN domain of reductase to interact with CYP2B4 to form a catalytically competent complex. Our study provides evidence that the length of the MBD-FMN domain linker is a major determinant of the ability of CYPOR to support CYP catalysis and drug metabolism by P450 enzymes.</p></div><div><h3>Preamble</h3><p>This manuscript is dedicated in memory of Dr. James R. Kincaid who was the doctoral advisor to Dr. Freeborn Rwere and a longtime collaborator and friend of Dr. Lucy Waskell. Dr. James R. Kincaid was a distinguished professor of chemistry specializing in resonance Raman (rR) studies of heme proteins. He inspired Dr. Rwere (a Zimbabwean native) and three other Zimbabweans (Dr. Remigio Usai, Dr. Daniel Kaluka and Ms. Munyaradzi E. Manyumwa) to use lasers to document subtle changes occurring at heme active site of globin proteins (myoglobin and hemoglobin) and cytochrome P450 enzymes. Dr. Rwere appreciate his contributions to the development of talented Black scientists from Africa.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"259 ","pages":"Article 112667"},"PeriodicalIF":3.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728650","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":"TAR RNA selective targeting ruthenium(II) complexes as HIV-1 reverse transcriptase inhibitors: On exploring structure-activity relationships of multiple positions","authors":"Meng Liu,&nbsp;Dan-Dan Xie,&nbsp;Yuan-Xiao Guo,&nbsp;Run-Yu Zhao,&nbsp;Fu-Dan Liu,&nbsp;Hongbin Zhang,&nbsp;Feng Gao","doi":"10.1016/j.jinorgbio.2024.112664","DOIUrl":"10.1016/j.jinorgbio.2024.112664","url":null,"abstract":"<div><p>HIV-1 reverse transcriptase (RT) inhibitors play a crucial role in the treatment of HIV by preventing the activity of the enzyme responsible for the replication of the virus. The HIV-1 Tat protein binds to transactivation response (TAR) RNA and recruits host factors to stimulate HIV-1 transcription. We have created a small library consisting of 4 × 6 polypyridyl Ru(II) complexes that selectively bind to TAR RNA, with targeting groups specific to HIV-1 TAR RNA. The molecule design was conducted by introducing hydroxyl or methoxy groups into an established potent TAR binder. The potential TAR binding ability was analysis from nature charge population and electrostatic potential by quantum chemistry calculations. Key modifications were found to be R₁ and R₃ groups. The most potent and selective TAR RNA binder was <strong>a3</strong> with R₁ = OH, R₂ = H and R₃ = Me. Through molecular recognition of hydrogen bonds and electrostatic attraction, they were able to firmly and selectively bind HIV-1 TAR RNA. Furthermore, they efficiently obstructed the contact between TAR RNA and Tat protein, and inhibited the reverse transcription activity of HIV-1 RT. The polypyridyl Ru(II) complexes were chemical and photo-stable, and sensitive and selective spectroscopic responses to TAR RNA. They exhibited little toxicity towards normal cells. Hence, this study might offer significant drug design approaches for researching AIDS and other illnesses associated with RT, including HCV, EBOV, and SARS-CoV-2. Moreover, it could contribute to fundamental research on the interactions of inorganic transition metal complexes with biomolecules.</p></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"259 ","pages":"Article 112664"},"PeriodicalIF":3.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632221","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":"8th Georgian Bay International Conference on Bioinorganic Chemistry (CanBIC-8)","authors":"Martin Stillman,&nbsp;John Dawson,&nbsp;Nagao Kobayashi,&nbsp;Zhifeng Ding","doi":"10.1016/j.jinorgbio.2024.112662","DOIUrl":"10.1016/j.jinorgbio.2024.112662","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"259 ","pages":"Article 112662"},"PeriodicalIF":3.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141703527","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}