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Nonprotonophoric Electrogenic Cl- Transport Mediated by Valinomycin-like Carriers

Lookup NU author(s): Dr Luke Judd

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

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 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.

Publication metadata

Author(s): Wu X, Judd LW, Howe ENW, Withecombe AM, Soto-Cerrato V, Li H, Busschaert N, Valkenier H, Perez-Tomas R, Sheppard DN, Jiang YB, Davis AP, Gale PA

Publication type: Article

Publication status: Published

Journal: Chem

Year: 2016

Volume: 1

Issue: 1

Pages: 127-146

Print publication date: 09/06/2016

Online publication date: 09/06/2016

Acceptance date: 23/03/2016

Date deposited: 15/03/2019

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.chempr.2016.04.002

DOI: 10.1016/j.chempr.2016.04.002

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