Nonprotonophoric electrogenic Cl− transport mediated by valinomycin-like carriers

Xin Wu, Luke Judd, Ethan N.W. Howe, Anne M. Withecombe, Vanessa Soto-Cerrato, Hongyu Li, Nathalie Busschaert, Hennie Valkenier-Van Dijk, Ricardo Pérez-Tomás, David Sheppard, Yun-Bao Jiang, Anthony Davis, Philip A. Gale

Research output: Contribution to journalArticle (Academic Journal)peer-review

116 Citations (Scopus)
362 Downloads (Pure)


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 identify 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 for the first time that a valinomycin equivalent for Cl− -selective transport is achievable.
Original languageEnglish
Pages (from-to)127-146
Number of pages20
Issue number1
Early online date9 Jun 2016
Publication statusPublished - 7 Jul 2016


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