Author: Hazel A. Sparkes

Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia.

2016

Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl)ureidodecalin shows especial…

Yellow fluorescent proteinpotencyGeneral Chemical Engineeringsynthetic anion carriersCystic Fibrosis Transmembrane Conductance Regulator01 natural sciencesMadin Darby Canine Kidney CellsCell membranedeliverabilityta116Drug CarriersbiologyMolecular StructureChemistryBiological activitypersistenceCystic fibrosis transmembrane conductance regulatorTransmembrane proteinanionophoresmedicine.anatomical_structureBiochemistryPhosphatidylcholinesSteroidsChlorineAnionsCell SurvivalNaphthalenesta3111010402 general chemistryDogsBacterial ProteinsCyclohexanesmedicineAnimalsHumansIon transporterCell ProliferationIon Transport010405 organic chemistryCell MembranetoxicityTransporterEpithelial CellsHydrogen BondingGeneral ChemistryRats Inbred F3440104 chemical sciencesElectrophysiological PhenomenaLuminescent ProteinsMicroscopy FluorescenceCell cultureDrug Designbiology.proteinHeLa CellsNature chemistry

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Anion Recognition by a Bioactive Diureidodecalin Anionophore: Solid-State, Solution, and Computational Studies

2018

Recent work has identified a bis-(p-nitrophenyl)ureidodecalin anion carrier as a promising candidate for biomedical applications, showing good activity for chloride transport in cells yet almost no cytotoxicity. To underpin further development of this and related compounds, a detailed structural and binding investigation is reported. Crystal structures of the transporter as five solvates confirm the diaxial positioning of urea groups while revealing a degree of conformational flexibility. Structures of complexes with Cl−, Br−, NO3 −, SO4 2− and AcO−, supported by computational studies, show how the binding site can adapt to accommodate these anions. 1H NMR binding studies revealed exception…

Anionsinorganic chemicalsMagnetic Resonance SpectroscopyAnion ReceptorsMolecular Conformationreceptorsanion recognitionCrystal structureCrystallography X-Ray010402 general chemistry01 natural sciencesChlorideCatalysisNitrophenolsComputers MolecularPhysico-chimie généraleChloridesChimie des colloïdesTheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITYmedicineUreaChimieMoleculehost–guest interactionsBinding siteta116Binding SitesFull Paper010405 organic chemistryChemistryHydrogen bondOrganic ChemistryChimie des surfaces et des interfacesGeneral ChemistryFull PapersAffinities0104 chemical sciences3. Good healthChimie organiqueCrystallographyhydrogen bondssolid-state structuresProton NMRSelectivityanionsmedicine.drugChemistry - A European Journal

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CCDC 1420195: Experimental Crystal Structure Determination

2015

Related Article: Hongyu Li, Hennie Valkenier, Luke W. Judd, Peter R. Brotherhood, Sabir Hussain, James A. Cooper, Ondřej Jurček, Hazel A. Sparkes, David N. Sheppard, Anthony P. Davis|2016|Nature Chemistry|8|24|doi:10.1038/nchem.2384

Space GroupCrystallographyCrystal SystemCrystal StructureCell ParametersNNNN-tetramethylaminium chloride ethyl 27-bis(((4-nitrophenyl)carbamoyl)amino)octahydronaphthalene-4a(2H)-carboxylateExperimental 3D Coordinates

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