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)

61 Citations (Scopus)
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Abstract

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
JournalChem
Volume1
Issue number1
Early online date9 Jun 2016
DOIs
Publication statusPublished - 7 Jul 2016

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    Wu, X., Judd, L., Howe, E. N. W., Withecombe, A. M., Soto-Cerrato, V., Li, H., Busschaert, N., Valkenier-Van Dijk, H., Pérez-Tomás, R., Sheppard, D., Jiang, Y-B., Davis, A., & Gale, P. A. (2016). Nonprotonophoric electrogenic Cl− transport mediated by valinomycin-like carriers. Chem, 1(1), 127-146. https://doi.org/10.1016/j.chempr.2016.04.002