Recent publication about nonprotonophoric electrogenic Cl− transport mediated by valinomycin-like carriers in Chem Journal in collaboration with Philip A. Gale group (University of Southampton).
2016 June 8
Title: Nonprotonophoric Electrogenic Cl− Transport Mediated by Valinomycin-like Carriers.
Authors: Wu X, Judd LW, Howe ENW, Withecombe AM, Soto-Cerrato V, Li H, Busschaert N, Valkenier H, Pérez-Tomás R, Sheppard DN, Jiang Y, Davis AP, and Gale PA.
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.