The University of Southampton
University of Southampton Institutional Repository

pH-regulated nonelectrogenic anion transport by phenylthiosemicarbazones

pH-regulated nonelectrogenic anion transport by phenylthiosemicarbazones
pH-regulated nonelectrogenic anion transport by phenylthiosemicarbazones
Gated ion transport across biological membrane is an intrinsic process regulated by protein channels. Synthetic anion carriers (anionophores) have potential applications in biological research, however, previous reported examples are mostly nonspecific, capable of mediating both electrogenic and electroneutral (non-electrogenic) 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 non-electrogenic, inseparable H+/Cl? cotransport. This study demonstrates the first examples of pH-switchable non-electrogenic anion transporters
0002-7863
8301-8308
Howe, Ethan
be05ae9a-02e0-443b-97b2-d65cc387af40
Busschaert, Nathalie
bf307f09-0a86-4a03-afd8-4b0a59a8f72b
Wu, Xin
65360fe8-d25a-4652-b7e4-40d513b57e7e
Berry, Stuart
c7287fbf-5845-4f28-b3ab-bf3a35e3fd9f
Ho, Junming
d5cc0225-1885-4e83-83e9-48438a385b70
Light, Mark
cf57314e-6856-491b-a8d2-2dffc452e161
Czech, Dawid
8dc3ff2a-7df7-47e4-be64-87d5446bdea7
Klein, Harry A.
3f9cb6fb-8aa5-4af2-acc0-968b0bd2ddc7
Kitchen, Jonathan
3999f5cb-d53e-4c51-b750-627bd2a1b9b6
Gale, Philip A.
c840b7e9-6847-4843-91af-fa0f8563d943
Howe, Ethan
be05ae9a-02e0-443b-97b2-d65cc387af40
Busschaert, Nathalie
bf307f09-0a86-4a03-afd8-4b0a59a8f72b
Wu, Xin
65360fe8-d25a-4652-b7e4-40d513b57e7e
Berry, Stuart
c7287fbf-5845-4f28-b3ab-bf3a35e3fd9f
Ho, Junming
d5cc0225-1885-4e83-83e9-48438a385b70
Light, Mark
cf57314e-6856-491b-a8d2-2dffc452e161
Czech, Dawid
8dc3ff2a-7df7-47e4-be64-87d5446bdea7
Klein, Harry A.
3f9cb6fb-8aa5-4af2-acc0-968b0bd2ddc7
Kitchen, Jonathan
3999f5cb-d53e-4c51-b750-627bd2a1b9b6
Gale, Philip A.
c840b7e9-6847-4843-91af-fa0f8563d943

Howe, Ethan, Busschaert, Nathalie, Wu, Xin, Berry, Stuart, Ho, Junming, Light, Mark, Czech, Dawid, Klein, Harry A., Kitchen, Jonathan and Gale, Philip A. (2016) pH-regulated nonelectrogenic anion transport by phenylthiosemicarbazones. Journal of the American Chemical Society, 138, 8301-8308. (doi:10.1021/jacs.6b04656).

Record type: Article

Abstract

Gated ion transport across biological membrane is an intrinsic process regulated by protein channels. Synthetic anion carriers (anionophores) have potential applications in biological research, however, previous reported examples are mostly nonspecific, capable of mediating both electrogenic and electroneutral (non-electrogenic) 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 non-electrogenic, inseparable H+/Cl? cotransport. This study demonstrates the first examples of pH-switchable non-electrogenic anion transporters

Text
Thiosemicarbazone_Manuscript_Final.docx - Accepted Manuscript
Download (1MB)
Text
jacs%2E6b04656.pdf - Version of Record
Available under License Creative Commons Attribution.
Download (3MB)

More information

Accepted/In Press date: 14 June 2016
e-pub ahead of print date: 24 June 2016

Identifiers

Local EPrints ID: 396898
URI: http://eprints.soton.ac.uk/id/eprint/396898
ISSN: 0002-7863
PURE UUID: ed844c88-795d-4b56-bfec-9396354b0691
ORCID for Mark Light: ORCID iD orcid.org/0000-0002-0585-0843
ORCID for Jonathan Kitchen: ORCID iD orcid.org/0000-0002-7139-5666
ORCID for Philip A. Gale: ORCID iD orcid.org/0000-0001-9751-4910

Catalogue record

Date deposited: 16 Jun 2016 13:15
Last modified: 15 Mar 2024 05:40

Export record

Altmetrics

Contributors

Author: Ethan Howe
Author: Nathalie Busschaert
Author: Xin Wu
Author: Stuart Berry
Author: Junming Ho
Author: Mark Light ORCID iD
Author: Dawid Czech
Author: Harry A. Klein
Author: Jonathan Kitchen ORCID iD
Author: Philip A. Gale ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×