pH-Regulated Nonelectrogenic Anion Transport by Phenylthiosemicarbazones

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• 作者：Ethan N. W. Howe ; Nathalie Busschaert ; Xin Wu ; Stuart N. Berry ; Junming Ho ; Mark E. Light ; Dawid D. Czech ; Harry A. Klein ; Jonathan A. Kitchen ; Philip A. Gale
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：July 6, 2016
• 年：2016
• 卷：138
• 期：26
• 页码：8301-8308
• 全文大小：599K
• 年卷期：0
• ISSN：1520-5126

文摘

Gated ion transport across biological membranes is an intrinsic process regulated by protein channels. Synthetic anion carriers (anionophores) have potential applications in biological research; however, previously reported examples are mostly nonspecific, capable of mediating both electrogenic and electroneutral (nonelectrogenic) transport processes. Here we show the transmembrane Cl^– transport studies of synthetic phenylthiosemicarbazones mimicking the function of acid-sensing (proton-gated) ion channels. These anionophores have remarkable pH-switchable transport properties with up to 640-fold increase in transport efficacy on going from pH 7.2 to 4.0. This “gated” process is triggered by protonation of the imino nitrogen and concomitant conformational change of the anion-binding thiourea moiety from anti to syn. By using a combination of two cationophore-coupled transport assays, with either monensin or valinomycin, we have elucidated the fundamental transport mechanism of phenylthiosemicarbazones which is shown to be nonelectrogenic, inseparable H⁺/Cl^– cotransport. This study demonstrates the first examples of pH-switchable nonelectrogenic anion transporters.