The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

QSAR analysis of substituent effects on tambjamine anion transporters

QSAR analysis of substituent effects on tambjamine anion transporters
QSAR analysis of substituent effects on tambjamine anion transporters
The transmembrane anion transport activity of 43 synthetic molecules based on the structure of marine alkaloid tambjamine were assessed in model phospholipid (POPC) liposomes. The anionophoric activity of these molecules showed a parabolic dependence with lipophilicity, with an optimum range for transport efficiency. Using a quantitative structure-transport activity (QSAR) approach it was possible to rationalize these results and to quantify the contribution of lipophilicity to the transport activity of these derivatives. While the optimal value of log P and the curvature of the parabolic dependence is a property of the membrane (and so similar for the different series of substituents) we found that for relatively simple substituents in certain locations on the tambjamine core, hydrophobic interactions clearly dominate, but for others, more specific interactions are present that change the position of the membrane hydrophobicity parabolic envelope.
1478-6524
1600-1608
Knight, Nicola J.
fbc21e18-095e-4c1a-a4bf-6277debf5c4b
Hernando, Elsa
b5599d93-8350-47e9-9abe-ecc124b9407a
Haynes, Cally J.E.
524040bd-57f9-4a5f-869d-55173c99ba16
Busschaert, Nathalie
bf307f09-0a86-4a03-afd8-4b0a59a8f72b
Clarke, Harriet J.
429f1f84-9527-4471-a9e8-1d52760dd01b
Takimoto, Koji
36f493e1-e814-42d4-99e4-b9c9b45438fa
García-Valverde, María
e5108ac4-fa66-417d-b2af-f3f63085287b
Frey, Jeremy G.
ba60c559-c4af-44f1-87e6-ce69819bf23f
Quesada, Roberto
c7db6299-4eb5-490d-9e6b-be4b9fbc8ca9
Gale, Philip A.
c840b7e9-6847-4843-91af-fa0f8563d943
Knight, Nicola J.
fbc21e18-095e-4c1a-a4bf-6277debf5c4b
Hernando, Elsa
b5599d93-8350-47e9-9abe-ecc124b9407a
Haynes, Cally J.E.
524040bd-57f9-4a5f-869d-55173c99ba16
Busschaert, Nathalie
bf307f09-0a86-4a03-afd8-4b0a59a8f72b
Clarke, Harriet J.
429f1f84-9527-4471-a9e8-1d52760dd01b
Takimoto, Koji
36f493e1-e814-42d4-99e4-b9c9b45438fa
García-Valverde, María
e5108ac4-fa66-417d-b2af-f3f63085287b
Frey, Jeremy G.
ba60c559-c4af-44f1-87e6-ce69819bf23f
Quesada, Roberto
c7db6299-4eb5-490d-9e6b-be4b9fbc8ca9
Gale, Philip A.
c840b7e9-6847-4843-91af-fa0f8563d943

Knight, Nicola J., Hernando, Elsa, Haynes, Cally J.E., Busschaert, Nathalie, Clarke, Harriet J., Takimoto, Koji, García-Valverde, María, Frey, Jeremy G., Quesada, Roberto and Gale, Philip A. (2016) QSAR analysis of substituent effects on tambjamine anion transporters. Chemical Science, 7 (2), 1600-1608. (doi:10.1039/C5SC03932K).

Record type: Article

Abstract

The transmembrane anion transport activity of 43 synthetic molecules based on the structure of marine alkaloid tambjamine were assessed in model phospholipid (POPC) liposomes. The anionophoric activity of these molecules showed a parabolic dependence with lipophilicity, with an optimum range for transport efficiency. Using a quantitative structure-transport activity (QSAR) approach it was possible to rationalize these results and to quantify the contribution of lipophilicity to the transport activity of these derivatives. While the optimal value of log P and the curvature of the parabolic dependence is a property of the membrane (and so similar for the different series of substituents) we found that for relatively simple substituents in certain locations on the tambjamine core, hydrophobic interactions clearly dominate, but for others, more specific interactions are present that change the position of the membrane hydrophobicity parabolic envelope.

Text
Manuscript.docx - Accepted Manuscript
Available under License Other.
Download (3MB)
Text
C5SC03932K.pdf - Version of Record
Available under License Other.
Download (810kB)
Text
authorreprints.pdf - Version of Record
Available under License Creative Commons Attribution.
Download (769kB)

More information

Accepted/In Press date: 17 November 2015
e-pub ahead of print date: 8 December 2015
Published date: 2016
Organisations: Organic Chemistry: SCF

Identifiers

Local EPrints ID: 384890
URI: http://eprints.soton.ac.uk/id/eprint/384890
ISSN: 1478-6524
PURE UUID: 8f8c15e1-0dee-4bd5-b4fc-cf3d29f4e819
ORCID for Nicola J. Knight: ORCID iD orcid.org/0000-0001-8286-3835
ORCID for Jeremy G. Frey: ORCID iD orcid.org/0000-0003-0842-4302
ORCID for Philip A. Gale: ORCID iD orcid.org/0000-0001-9751-4910

Catalogue record

Date deposited: 13 Jan 2016 15:28
Last modified: 21 Nov 2021 03:29

Export record

Altmetrics

Contributors

Author: Nicola J. Knight ORCID iD
Author: Elsa Hernando
Author: Cally J.E. Haynes
Author: Nathalie Busschaert
Author: Harriet J. Clarke
Author: Koji Takimoto
Author: María García-Valverde
Author: Jeremy G. Frey ORCID iD
Author: Roberto Quesada
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.

×