-
Journal of Biological Inorganic... Jun 2020The association of proteins with metals, metalation, is challenging because the tightest binding metals are rarely the correct ones. Inside cells, correct metalation is... (Review)
Review
The association of proteins with metals, metalation, is challenging because the tightest binding metals are rarely the correct ones. Inside cells, correct metalation is enabled by controlled bioavailability plus extra mechanisms for tricky combinations such as iron and manganese.
Topics: Biological Availability; Chemistry, Bioinorganic; Humans; Metals, Heavy; Proteins
PubMed: 32333210
DOI: 10.1007/s00775-020-01790-3 -
Anti-cancer Agents in Medicinal... Aug 2022Metal based therapy is no new in biomedical research. In early days, the biggest limitation was the inequality among therapeutical and toxicological dosages. Ever since,...
Metal based therapy is no new in biomedical research. In early days, the biggest limitation was the inequality among therapeutical and toxicological dosages. Ever since, Barnett Rosenberg discovered cisplatin, a new era has begun to treat cancer with metal complexes. Platinum complexes such as oxaliplatin, cisplatin, and carboplatin, seem to be the foundation of metal/s-based components to challenge malignancies. With advancement in the biomolemoecular mechanism, researchers have started developing non-classical platinum-based complexes, where a different mechanistic approach of the complexes is observed towards the biomolecular target. Till date, larger numbers of metal/s-based complexes were synthesized by overhauling the present structures chemically by substituting the ligand or preparing the whole novel component with improved cytotoxic and safety profiles. Howsoever, due to elevated accentuation upon the therapeutic importance of metal/s-based components, a couple of those agents are at present in clinical trials and several other are in anticipating regulatory endorsement to enter the trial. This literature highlights the detailed heterometallic multinuclear components, primarily focusing on platinum, ruthenium, gold and remarks on possible stability, synergism, mechanistic studies and structure activity relationships.
Topics: Antineoplastic Agents; Cisplatin; Coordination Complexes; Humans; Neoplasms; Platinum; Ruthenium
PubMed: 35362388
DOI: 10.2174/1871520622666220331085144 -
Advanced Materials (Deerfield Beach,... Sep 2019The rapid development of flexible and wearable electronics favors low-cost, solution-processing, and high-throughput techniques for fabricating metal contacts,... (Review)
Review
The rapid development of flexible and wearable electronics favors low-cost, solution-processing, and high-throughput techniques for fabricating metal contacts, interconnects, and electrodes on flexible substrates of different natures. Conventional top-down printing strategies with metal-nanoparticle-formulated inks based on the thermal sintering mechanism often suffer from overheating, rough film surface, low adhesion, and poor metal quality, which are not desirable for most flexible electronic applications. In recent years, a bottom-up strategy termed as polymer-assisted metal deposition (PAMD) shows great promise in addressing the abovementioned challenges. Here, a detailed review of the development of PAMD in the past decade is provided, covering the fundamental chemical mechanism, the preparation of various soft and conductive metallic materials, the compatibility to different printing technologies, and the applications for a wide variety of flexible and wearable electronic devices. Finally, the attributes of PAMD in comparison with conventional nanoparticle strategies are summarized and future technological and application potentials are elaborated.
Topics: Mechanical Phenomena; Metals; Polymers; Printing; Wearable Electronic Devices
PubMed: 31304644
DOI: 10.1002/adma.201902987 -
Journal of Inorganic Biochemistry Jul 2023Precise metal-protein coordination by design remains a considerable challenge. Polydentate, high-metal-affinity protein modifications, both chemical and recombinant, can...
Precise metal-protein coordination by design remains a considerable challenge. Polydentate, high-metal-affinity protein modifications, both chemical and recombinant, can enable metal localization. However, these constructs are often bulky, conformationally and stereochemically ill-defined, or coordinately saturated. Here, we expand the biomolecular metal-coordination toolbox with the irreversible attachment to cysteine of bis(1-methylimidazol-2-yl)ethene ("BMIE"), which generates a compact imidazole-based metal-coordinating ligand. Conjugate additions of small-molecule thiols (thiocresol and N-Boc-Cys) with BMIE confirm general thiol reactivity. The BMIE adducts are shown to complex the divalent metal ions Cu and Zn in bidentate (N) and tridentate (NS*) coordination geometries. Cysteine-targeted BMIE modification (>90% yield at pH 8.0) of a model protein, the S203C variant of carboxypeptidase G2 (CPG2), measured with ESI-MS, confirms its utility as a site-selective bioconjugation method. ICP-MS analysis confirms mono-metallation of the BMIE-modified CPG2 protein with Zn, Cu, and Co. EPR characterization of the BMIE-modified CPG2 protein reveals the structural details of the site selective 1:1 BMIE-Cu coordination and symmetric tetragonal geometry under physiological conditions and in the presence of various competing and exchangeable ligands (HO/HO, tris, and phenanthroline). An X-ray protein crystal structure of BMIE-modified CPG2-S203C demonstrates that the BMIE modification is minimally disruptive to the overall protein structure, including the carboxypeptidase active sites, although Zn metalation could not be conclusively discerned at the resolution obtained. The carboxypeptidase catalytic activity of BMIE-modified CPG2-S203C was also assayed and found to be minimally affected. These features, combined with ease of attachment, define the new BMIE-based ligation as a versatile metalloprotein design tool, and enable future catalytic and structural applications.
Topics: Metalloproteins; Cysteine; Zinc; Metals; Peptide Hydrolases; Imidazoles; Sulfhydryl Compounds; Copper; Crystallography, X-Ray; Ligands
PubMed: 37030124
DOI: 10.1016/j.jinorgbio.2023.112206 -
Toxicology Letters Oct 2021The metal/metal alloy-based implants and prostheses are in use for over a century, and the rejections, revisions, and metal particle-based toxicities were reported... (Review)
Review
The metal/metal alloy-based implants and prostheses are in use for over a century, and the rejections, revisions, and metal particle-based toxicities were reported concurrently. Complications developed due to metal ions, metal debris, and organo-metallic particles in orthopedic patients have been a growing concern in recent years. It was reported that local and systemic toxicity caused by such released products from the implants is one of the major reasons for implant rejection and revision. Even though the description of environmental metal toxicants and safety limits for their exposure to humans were well established in the literature, an effort was not adequately performed in the case of implant-based metal toxicology. Since the metal ion concentration in serum acts as a possible indicator of the systemic toxicity, this review summarizes the reported human serum safe limits, toxic limits, and concentration range (μg/L, ppb, etc.) for mild to severe symptoms of six (cardiac, hepatic, neuro, nephron, dermal and endocrine) systemic toxicities for twelve most commonly used metallic implants. It also covers the widely used metal ion quantification techniques and systemic toxicity treatments reported.
Topics: Adult; Aged; Aged, 80 and over; Cardiotoxicity; Female; Heavy Metal Poisoning; Humans; Ions; Male; Metals; Middle Aged; Prostheses and Implants
PubMed: 34252509
DOI: 10.1016/j.toxlet.2021.07.004 -
Current Topics in Medicinal Chemistry 2015The spectacular progress of research in the nanotechnology field led to the achievement of important knowledge of materials at the atomic and molecular scale and the... (Review)
Review
The spectacular progress of research in the nanotechnology field led to the achievement of important knowledge of materials at the atomic and molecular scale and the extent of the use of nanoparticles in the design of medical products, ecological processes, cosmetics and other biotechnological applications. One of the current focuses of the medical applications of nanotechnology is the development of new strategies to inhibit the activity of different microorganisms. The purpose of this review was to present the antimicrobial activity of metal cations in micro- and nanoparticulate forms and the dependence of this biological activity on shape, size and physico-chemical conditions.
Topics: Anti-Infective Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Metal Nanoparticles; Metals, Heavy; Nanotechnology; Particle Size
PubMed: 25877091
DOI: 10.2174/1568026615666150414125015 -
Journal of Investigational Allergology... 2016The use of metals in the medical field has become increasingly prevalent over the past few decades. Patients find themselves being exposed to metals in a variety of... (Review)
Review
The use of metals in the medical field has become increasingly prevalent over the past few decades. Patients find themselves being exposed to metals in a variety of ways, ranging from external exposure to instruments such as the stainless steel in surgical blades to internal exposure via medical devices being implanted in their bodies. There has been growing interest in the possibility of developing hypersensitivity reactions to constituent metals in medical implant devices, both in cutaneous and systemic forms. Hypersensitivity reactions to metals are uncommon, but they are reported and require appropriate evaluation and management, particularly if they are symptomatic. In view of the lack of consensus in the field on the appropriate steps to evaluate and manage patients with suspected metal hypersensitivity reactions, this review aims to analyze current evidence on hypersensitivity reactions to metallic implants in orthopedic surgery, endovascular surgery, obstetrics and gynecology, and dental surgery.
Topics: Humans; Hypersensitivity; Metals; Prostheses and Implants
PubMed: 27763855
DOI: 10.18176/jiaci.0095 -
The Journal of Biological Chemistry Dec 2022The heterodimerization of WT Cu, Zn superoxide dismutase-1 (SOD1), and mutant SOD1 might be a critical step in the pathogenesis of SOD1-linked amyotrophic lateral...
The heterodimerization of WT Cu, Zn superoxide dismutase-1 (SOD1), and mutant SOD1 might be a critical step in the pathogenesis of SOD1-linked amyotrophic lateral sclerosis (ALS). Rates and free energies of heterodimerization (ΔG) between WT and ALS-mutant SOD1 in mismatched metalation states-where one subunit is metalated and the other is not-have been difficult to obtain. Consequently, the hypothesis that under-metalated SOD1 might trigger misfolding of metalated SOD1 by "stealing" metal ions remains untested. This study used capillary zone electrophoresis and mass spectrometry to track heterodimerization and metal transfer between WT SOD1, ALS-variant SOD1 (E100K, E100G, D90A), and triply deamidated SOD1 (modeled with N26D/N131D/N139D substitutions). We determined that rates of subunit exchange between apo dimers and metalated dimers-expressed as time to reach 30% heterodimer-ranged from t = 67.75 ± 9.08 to 338.53 ± 26.95 min; free energies of heterodimerization ranged from ΔG = -1.21 ± 0.31 to -3.06 ± 0.12 kJ/mol. Rates and ΔG values of partially metalated heterodimers were more similar to those of fully metalated heterodimers than apo heterodimers, and largely independent of which subunit (mutant or WT) was metal-replete or metal-free. Mass spectrometry and capillary electrophoresis demonstrated that mutant or WT 4Zn-SOD1 could transfer up to two equivalents of Zn to mutant or WT apo-SOD1 (at rates faster than the rate of heterodimerization). This result suggests that zinc-replete SOD1 can function as a chaperone to deliver Zn to apo-SOD1, and that WT apo-SOD1 might increase the toxicity of mutant SOD1 by stealing its Zn.
Topics: Humans; Superoxide Dismutase-1; Amyotrophic Lateral Sclerosis; Superoxide Dismutase; Metals; Zinc; Mutation
PubMed: 36265587
DOI: 10.1016/j.jbc.2022.102610 -
Journal of the American Chemical Society Jun 2021Metal nanostructures of chiral geometry interacting with light via surface plasmon resonances can produce tailorable optical activity with their structural alterations....
Metal nanostructures of chiral geometry interacting with light via surface plasmon resonances can produce tailorable optical activity with their structural alterations. However, bottom-up fabrication of arbitrary chiral metal nanostructures with precise size and morphology remains a synthetic challenge. Here we develop a DNA origami-enabled aqueous solution metallization strategy to prescribe the chirality of silver nanostructures in three dimensions. We find that diamine silver(I) complexes coordinate with the bases of prescribed single-stranded protruding clustered DNA (pcDNA) on DNA origami via synergetic interactions including coordination, hydrogen bonds, and ion-π interaction, which induce site-specific pcDNA condensation and local enrichment of silver precursors that lowers the activation energy for nucleation. Using tubular DNA origami-based metallization, we obtain helical silver patterns up to a micrometer in length with well-defined chirality and pitches. We further demonstrate tailorable plasmonic optical activity of metallized chiral silver nanostructures. This method opens new pathways to synthesize programmable inorganic materials with arbitrary morphology and chirality.
Topics: DNA; Hydrogen Bonding; Metal Nanoparticles; Particle Size; Silver
PubMed: 34078072
DOI: 10.1021/jacs.1c00363 -
Journal of Inorganic Biochemistry Dec 2023The flexibility of mammalian metallothioneins (MTs) has contributed to the difficulty in obtaining structural information for this family of metalloproteins that bind...
The flexibility of mammalian metallothioneins (MTs) has contributed to the difficulty in obtaining structural information for this family of metalloproteins that bind divalent metals with its twenty cysteines. While the two-domain structure for CdMT is well-established as a CdS and CdS, a third structure has been reported when 8 Cd(II) ions bind to MT1. Isoform 3 of the MT family, MT3, has been of interest to the research community since its isolation as a growth inhibitory factor isolated in brain tissue, and has since been noted as a prominent participant in the mediation of neurodegenerative diseases and regular brain development. The differences between MT3 and the other isoforms of MT include an additional hexapeptide insertion of acidic residues in the α domain as well as the introduction of two prolines in the β domain. It is unclear whether these changes impact the metalation properties of MT3. We report the formation of a CdMT3 species is characterized by electrospray ionization mass spectrometry and UV-visible absorption spectroscopy. We report that the spectroscopic properties of this supermetalated CdMT3 are similar to those of the supermetalated CdMT1, with a clear indication of changes in structure from "fully-metalated" CdMT3 to supermetalated CdMT3 from circular dichroism spectra and both 1D Cd and 2D H-Cd HSQC NMR spectra. We conclude that the metalation properties are not impacted significantly due to the amino acid changes in MT3, and that the cysteinyl thiols are the key players in determining the capacity of metal-binding and the structure of metal-thiolate clusters.
Topics: Humans; Animals; Metallothionein 3; Cadmium; Metals; Metallothionein; Circular Dichroism; Mammals
PubMed: 37832463
DOI: 10.1016/j.jinorgbio.2023.112392