The University of Southampton
University of Southampton Institutional Repository

Nonprotonophoric electrogenic chloride transport mediated by valinomycin-like carriers

Nonprotonophoric electrogenic chloride transport mediated by valinomycin-like carriers
Nonprotonophoric electrogenic chloride transport mediated by valinomycin-like carriers
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 identify 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 for the first time that a valinomycin equivalent for Cl?-selective transport is achievable.
127-146
Wu, Xin
65360fe8-d25a-4652-b7e4-40d513b57e7e
Judd, Luke
8389d141-8218-4113-b809-7f8f67f0bc79
Howe, Ethan
be05ae9a-02e0-443b-97b2-d65cc387af40
Withecombe, Anne
a7832769-2ae9-4eb2-9d7d-d960906fc85f
Soto-Cerrato, Vanessa
d14f15d9-a8f6-4a9a-9be8-f27417482712
Li, Hongyu
ecf34b99-1d3d-49c1-be7b-5edee54a6a2e
Busschaert, Nathalie
bf307f09-0a86-4a03-afd8-4b0a59a8f72b
Valkenier, Hennie
b9599ae0-1740-495b-a00e-841e7552e1bc
Perez-Tomas, Ricardo
f845aa66-dab9-4266-9ad4-8ee8b0d792d4
Sheppard, David
f4464abe-f70b-41e4-88c7-8e6c93c98e86
Jiang, Yun-Bao
d7717409-7411-4027-97ce-218de4ff6b18
Davis, Anthony
ebd8d676-c7b9-4c7f-8782-40169ef9497d
Gale, Philip
c840b7e9-6847-4843-91af-fa0f8563d943
Wu, Xin
65360fe8-d25a-4652-b7e4-40d513b57e7e
Judd, Luke
8389d141-8218-4113-b809-7f8f67f0bc79
Howe, Ethan
be05ae9a-02e0-443b-97b2-d65cc387af40
Withecombe, Anne
a7832769-2ae9-4eb2-9d7d-d960906fc85f
Soto-Cerrato, Vanessa
d14f15d9-a8f6-4a9a-9be8-f27417482712
Li, Hongyu
ecf34b99-1d3d-49c1-be7b-5edee54a6a2e
Busschaert, Nathalie
bf307f09-0a86-4a03-afd8-4b0a59a8f72b
Valkenier, Hennie
b9599ae0-1740-495b-a00e-841e7552e1bc
Perez-Tomas, Ricardo
f845aa66-dab9-4266-9ad4-8ee8b0d792d4
Sheppard, David
f4464abe-f70b-41e4-88c7-8e6c93c98e86
Jiang, Yun-Bao
d7717409-7411-4027-97ce-218de4ff6b18
Davis, Anthony
ebd8d676-c7b9-4c7f-8782-40169ef9497d
Gale, Philip
c840b7e9-6847-4843-91af-fa0f8563d943

Wu, Xin, Judd, Luke, Howe, Ethan, Withecombe, Anne, Soto-Cerrato, Vanessa, Li, Hongyu, Busschaert, Nathalie, Valkenier, Hennie, Perez-Tomas, Ricardo, Sheppard, David, Jiang, Yun-Bao, Davis, Anthony and Gale, Philip (2016) Nonprotonophoric electrogenic chloride transport mediated by valinomycin-like carriers. Chem, 1 (1), 127-146. (doi:10.1016/j.chempr.2016.04.002).

Record type: Article

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 identify 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 for the first time that a valinomycin equivalent for Cl?-selective transport is achievable.

Text
Gale article.pdf - Version of Record
Available under License Other.
Download (2MB)
Text
PIIS245192941630002X.pdf - Other
Download (2MB)

More information

Accepted/In Press date: 22 March 2016
e-pub ahead of print date: 9 June 2016
Published date: 7 July 2016
Organisations: Organic Chemistry: SCF

Identifiers

Local EPrints ID: 390321
URI: http://eprints.soton.ac.uk/id/eprint/390321
PURE UUID: bc9c5d8b-c779-4a9a-822d-beda2b0366f6
ORCID for Philip Gale: ORCID iD orcid.org/0000-0001-9751-4910

Catalogue record

Date deposited: 23 Mar 2016 14:33
Last modified: 15 Mar 2024 03:06

Export record

Altmetrics

Contributors

Author: Xin Wu
Author: Luke Judd
Author: Ethan Howe
Author: Anne Withecombe
Author: Vanessa Soto-Cerrato
Author: Hongyu Li
Author: Nathalie Busschaert
Author: Hennie Valkenier
Author: Ricardo Perez-Tomas
Author: David Sheppard
Author: Yun-Bao Jiang
Author: Anthony Davis
Author: Philip 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.

×