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Nonprotonophoric Electrogenic Cl- Transport Mediated by Valinomycin-like Carriers

par Wu, Xin;Judd, Luke W.;Howe, Ethan N. W.;Withecombe, Anne M.;Soto-Cerrato, Vanessa;Li, Hongyu;Busschaert, Nathalie;Valkenier, Hennie ;Pérez-Tomás, Ricardo;Sheppard, David N.;Jiang, Yun-Bao;Davis, Anthony P.;Gale, Philip A.
Référence Chem, 1, page (127-146)
Publication Publié, 2016-07-07

Article révisé par les pairs

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Résumé :

Synthetic transmembrane anion transporters (anionophores) have potential as tools for biomedical research and as therapeutic agents for diseases associated with anion-channel dysfunction. However, the possibility of H+ or OH- transport by anionophores has received little attention, and an anionophore selective for Cl- over H+/OH- is currently unavailable. Here, we show that depending on anionophore acidity, many anionophores facilitate electrogenic H+ or OH- transport, potentially leading to toxicity. Nevertheless, using several liposome-membrane-based assays, we identified two newly developed small molecules that promote electrogenic Cl- transport without effectively dissipating the transmembrane pH gradient, essentially mimicking the electrogenic cationophore valinomycin. The Cl- > H+/OH- selectivity of anionophores showed a consistent positive correlation with the degree of Cl- encapsulation and a negative correlation with the acidity of hydrogen-bond donors. Our study demonstrates that a valinomycin equivalent for Cl--selective transport is achievable.