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Carbonic Anhydrases and Metabolism
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Year: 2019 Publisher: Basel : MDPI - Multidisciplinary Digital Publishing Institute,

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Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism.


Book
Carbonic Anhydrases and Metabolism
Author:
Year: 2019 Publisher: Basel : MDPI - Multidisciplinary Digital Publishing Institute,

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Abstract

Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism.


Book
Carbonic Anhydrases and Metabolism
Author:
Year: 2019 Publisher: Basel : MDPI - Multidisciplinary Digital Publishing Institute,

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Bookmark

Abstract

Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism.


Book
Carbonic anhydrases : biochemistry and pharmacology of an evergreen pharmaceutical target
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ISBN: 0128167459 012816476X 9780128167458 9780128164761 Year: 2019 Publisher: London, England : Academic Press,

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Book
Carbonic Anhydrase as Drug Target : Thermodynamics and Structure of Inhibitor Binding
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ISBN: 303012780X 3030127788 Year: 2019 Publisher: Cham : Springer International Publishing : Imprint: Springer,

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This book offers deep insights into the thermodynamics and molecular structures of the twelve catalytically active isoforms of human carbonic anhydrase (CA) with a particular focus on inhibitor binding for drug design. X-ray crystallographic structures in combination with enzyme kinetic testing provide information on the interaction of CAs and their inhibitors, knowledge which is crucial for rational drug design. CAs are zinc carrying enzymes that catalyse the reversible interconversion of carbon dioxide and bicarbonate and are involved in numerous cellular processes. They are therefore a common target for drugs. The suppression of CA activities through inhibitory compounds has found application for example in diuretics and in glaucoma therapy. In this book methods used to determine binding thermodynamics of inhibitory compounds (Isothermal titration calorimetry, Fluorescent thermal shift assay/differential scanning fluorimetry and others) will be compared in detail. Also types and chemical synthesis of CA inhibitors, the use of antibodies against CAs as well as inhibitor application in animals are discussed. .


Book
Mineral Surface Reactions at the Nanoscale
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ISBN: 3038978973 3038978965 Year: 2019 Publisher: MDPI - Multidisciplinary Digital Publishing Institute

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Reactions at mineral surfaces are central to all geochemical processes. As minerals comprise the rocks of the Earth, the processes occurring at the mineral–aqueous fluid interface control the evolution of the rocks and hence the structure of the crust of the Earth during processes such as metamorphism, metasomatism, and weathering. In recent years focus has been concentrated on mineral surface reactions made possible through the development of advanced analytical methods such as atomic force microscopy (AFM), advanced electron microscopies (SEM and TEM), phase shift interferometry, confocal Raman spectroscopy, and advanced synchrotron-based applications, to enable mineral surfaces to be imaged and analyzed at the nanoscale. Experiments are increasingly complemented by molecular simulations to confirm or predict the results of these studies. This has enabled new and exciting possibilities to elucidate the mechanisms that govern mineral–fluid reactions. In this Special Issue, “Mineral Surface Reactions at the Nanoscale”, we present 12 contributions that highlight the role and importance of mineral surfaces in varying fields of research.


Book
Targets, Tracers and Translation - Novel Radiopharmaceuticals Boost Nuclear Medicine
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ISBN: 3039213148 303921313X Year: 2019 Publisher: MDPI - Multidisciplinary Digital Publishing Institute

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This is the fourth Special Issue in Pharmaceuticals within the last six years dealing with aspects of radiopharmaceutical sciences. It demonstrates the significant interest and increasing relevance to ameliorate nuclear medicine imaging with PET or SPECT, and also radiotherapeutical procedures.Numerous targets and mechanisms have been identified and have been under investigation over the previous years, covering many fields of medical and clinical research. This development is well illustrated by the articles in the present issue, including 13 original research papers and one review, covering a broad range of actual research topics in the field of radiopharmaceutical sciences.

Keywords

n/a --- pretargeting --- radioiodination --- neurodegeneration --- phosphoramidon --- GRPR --- molecular imaging --- allosteric modulator --- radiosynthesis --- separation --- ?-CIT. --- PET/CT imaging --- technetium-99m --- gastrin-releasing peptide receptor --- metabotropic glutamate receptor subtype 5 --- glutamate --- oncogenic fusions --- Fusarinine C --- hypoxia --- tirapazamine (TPZ) --- 68Ga --- sentinel lymph node --- 99mTc-radioligand --- iodine-131 --- electrophilic radioiodination --- 4-dioxide (BTDO) --- minigastrin --- ceftriaxone --- tropomyosin receptor kinase --- carbonic anhydrase IX --- ABP688 --- NPY(Y1)R --- MMPEP --- radiosensitizer --- neprilysin-inhibition --- radiochemistry --- girentuximab --- benzotriazine-1 --- gallium-68 --- cholecystokinin-2 receptor --- tumor targeting --- radioimmunotherapy --- salivary gland uptake --- metabolic stability --- tumor hypoxia --- multimerization --- oxidizing agent --- neuroinflammation --- gastrin-releasing peptide --- dextran --- carbon-11 --- peptide heterodimers --- apparent molar activity --- radiometals --- microglia --- rituximab --- [18F]FMISO --- [11C]meta-hydroxyephedrine --- Iodo-Gen® --- mannose --- 177Lu-radiopharmaceuticals --- azomycin nucleosides --- breast cancer --- click chemistry --- small animal imaging --- SR 4317 --- benzotriazine-1-monoxide (BTMO) --- bombesin --- prostate cancer --- Chloramine T --- 99mTc-radiopharmaceuticals --- ketamine --- PSMA-617 --- positron emission tomography --- hydrazinonicotinic acid (HYNIC) --- renal cell carcinomas --- [18F]PSS232 --- PET --- endoradiotherapy


Book
Biological Crystallization
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ISBN: 3039214047 3039214039 Year: 2019 Publisher: MDPI - Multidisciplinary Digital Publishing Institute

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For at least six hundred million years, life has been a fascinating laboratory of crystallization, referred to as biomineralization. During this huge lapse of time, many organisms from diverse phyla have developed the capability to precipitate various types of minerals, exploring distinctive pathways for building sophisticated structural architectures for different purposes. The Darwinian exploration was performed by trial and error, but the success in terms of complexity and efficiency is evident. Understanding the strategies that those organisms employ for regulating the nucleation, growth, and assembly of nanocrystals to build these sophisticated devices is an intellectual challenge and a source of inspiration in fields as diverse as materials science, nanotechnology, and biomedicine. However, “Biological Crystallization” is a broader topic that includes biomineralization, but also the laboratory crystallization of biological compounds such as macromolecules, carbohydrates, or lipids, and the synthesis and fabrication of biomimetic materials by different routes. This Special Issue collects 15 contributions ranging from biological and biomimetic crystallization of calcium carbonate, calcium phosphate, and silica-carbonate self-assembled materials to the crystallization of biological macromolecules. Special attention has been paid to the fundamental phenomena of crystallization (nucleation and growth), and the applications of the crystals in biomedicine, environment, and materials science.

Keywords

chitosan --- Csep1p --- bond selection during protein crystallization --- bioremediation --- education --- reductants --- heavy metals --- biomimetic crystallization --- MTT assay --- protein crystallization --- drug discovery --- optimization --- polymyxin resistance --- lysozyme --- ependymin-related protein (EPDR) --- equilibration between crystal bond and destructive energies --- barium carbonate --- dyes --- microseed matrix screening --- nanoapatites --- colistin resistance --- Haloalkane dehalogenase --- diffusion --- polyacrylic acid --- random microseeding --- protein ‘affinity’ to water --- insulin --- protein crystal nucleation --- agarose --- lithium ions --- ependymin (EPN) --- {00.1} calcite --- seeding --- Campylobacter consisus --- metallothioneins --- Crohn’s disease --- balance between crystal bond energy and destructive surface energies --- color change --- microbially induced calcite precipitation (MICP) --- crystallization of macromolecules --- crystallization --- calcein --- MCR-1 --- Cry protein crystals --- L-tryptophan --- circular dichroism --- crystal violet --- nanocomposites --- halide-binding site --- calcium carbonate --- PCDA --- ultrasonic irradiation --- adsorption --- biochemical aspects of the protein crystal nucleation --- GTL-16 cells --- proteinase k --- neutron protein crystallography --- classical and two-step crystal nucleation mechanisms --- thermodynamic and energetic approach --- heavy metal contamination --- N-acetyl-D-glucosamine --- crystallization in solution flow --- solubility --- biomorphs --- droplet array --- biomimetic materials --- ferritin --- biomineralization --- wastewater treatment --- H3O+ --- silica --- graphene --- supersaturation dependence of the crystal nucleus size --- pyrrole --- micro-crystals --- nucleation --- crystallography --- mammalian ependymin-related protein (MERP) --- high-throughput --- vaterite transformation --- gradients --- materials science --- bioprecipitation --- biomedicine --- human carbonic anhydrase IX --- protein crystal nucleation in pores --- growth --- crystal growth

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