pH-Regulated Nonelectrogenic Anion Transport by Phenylthiosemicarbazones.
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.
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Ethan N W
EN
Howe
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Nathalie
N
Busschaert
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Xin
X
Wu
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Stuart N
SN
Berry
Institute of High Performance Computing, Agency for Science Technology and Research , 1 Fusionopolis Way, #16-16, Connexis, Singapore 138632.
Junming
J
Ho
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Mark E
ME
Light
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Dawid D
DD
Czech
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Harry A
HA
Klein
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Jonathan A
JA
Kitchen
Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Philip A
PA
Gale