Journal of the American Chemical Society · 2021 · 102 citations · 32 references
Natural SciencesBiophysicsPharmacologyDrug DiscoveryIon Channel BiophysicsStructural BiologyChannel StructureChannelopathiesIon Channel PhysiologyIon ChannelsIon SelectivityPotassium Channel BiophysicsIon Channel EngineeringIon Channel Protein FoldingIon Channel SelectivityIon Channel Structure-function RelationshipsIon TransportPotassium Channel PharmacologyPotassium Channel PhysiologyTransport Selectivity
Small molecules that independently perform natural channel-like functions show greatly potential in the treatment of human diseases. Taking advantage of aromatic helical scaffolds, we develop a kind of foldamer-based ion channels with lumen size varying from 3.8 to 2.3 Å through a sequence substitution strategy. Our results clearly elucidate the importance of channel size in ion transport selectivity in molecular detail, eventually leading to the discoveries of the best artificial K+ channel by far and a rare sodium-preferential channel as well. High K+ selectivity and transport activity together make foldamers promising in therapeutic applications.
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The crystal structure of a voltage-gated sodium channel
Jian Payandeh, Todd Scheuer, Ning Zheng et al. · Nature · 2011 · 1.4K citations