6533b7d8fe1ef96bd126acec
RESEARCH PRODUCT
Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia.
Hennie ValkenierAnthony P. DavisSabir HussainDavid N. SheppardOndřej JurčekOndřej JurčekHazel A. SparkesHongyu LiLuke W. JuddPeter R. BrotherhoodJames A. Coopersubject
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 Cellsdescription
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 especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-01 | Nature chemistry |