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Nonprotonophoric electrogenic Cl− transport mediated by valinomycin-like carriers

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)127-146
Number of pages20
JournalChem
Volume1
Issue number1
Early online date9 Jun 2016
DOIs
DateAccepted/In press - 22 Mar 2016
DateE-pub ahead of print - 9 Jun 2016
DatePublished (current) - 7 Jul 2016

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.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Elsevier at http://www.sciencedirect.com/science/article/pii/S245192941630002X. Please refer to any applicable terms of use of the publisher.

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