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.
1600-1608
Knight, Nicola J.
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Hernando, Elsa
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Haynes, Cally J.E.
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Busschaert, Nathalie
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Clarke, Harriet J.
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Takimoto, Koji
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García-Valverde, María
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Frey, Jeremy G.
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Quesada, Roberto
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Gale, Philip A.
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2016
Knight, Nicola J.
fbc21e18-095e-4c1a-a4bf-6277debf5c4b
Hernando, Elsa
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Haynes, Cally J.E.
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Busschaert, Nathalie
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Clarke, Harriet J.
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Takimoto, Koji
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García-Valverde, María
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Frey, Jeremy G.
ba60c559-c4af-44f1-87e6-ce69819bf23f
Quesada, Roberto
c7db6299-4eb5-490d-9e6b-be4b9fbc8ca9
Gale, Philip A.
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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), .
(doi:10.1039/C5SC03932K).
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.
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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
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Date deposited: 13 Jan 2016 15:28
Last modified: 15 Mar 2024 04:05
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Contributors
Author:
Nicola J. Knight
Author:
Elsa Hernando
Author:
Cally J.E. Haynes
Author:
Nathalie Busschaert
Author:
Harriet J. Clarke
Author:
Koji Takimoto
Author:
María García-Valverde
Author:
Roberto Quesada
Author:
Philip A. Gale
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