Please use this identifier to cite or link to this item:
http://hdl.handle.net/10773/21002
Title: | Tilting and Tumbling in Transmembrane Anion Carriers: Activity Tuning through n-Alkyl Substitution |
Author: | Edwards, Sophie J. Marques, Igor Dias, Christopher M. Tromans, Robert A. Lees, Nicholas R. Felix, Vitor Valkenier, Hennie Davis, Anthony P. |
Keywords: | MOLECULAR-DYNAMICS SIMULATIONS CHLORIDE TRANSPORT FORCE-FIELD RECEPTORS AMBER LIPOPHILICITY ANIONOPHORES EXTRACTION PRINCIPLE MEMBRANES |
Issue Date: | 2016 |
Publisher: | WILEY-V C H VERLAG GMBH |
Abstract: | Anion transport by synthetic carriers (anionophores) holds promise for medical applications, especially the treatment of cystic fibrosis. Among the factors which determine carrier activity, the size and disposition of alkyl groups is proving remarkably important. Herein we describe a series of dithioureidodecalin anionophores, in which alkyl substituents on one face are varied from C-0 to C-10 in two-carbon steps. Activities increase then decrease as the chain length grows, peaking quite sharply at C-6. Molecular dynamics simulations showed the transporter chloride complexes releasing chloride as they approach the membrane-aqueous interface. The free transporter then stays at the interface, adopting an orientation that depends on the alkyl substituent. If chloride release is prevented, the complex is positioned similarly. Longer chains tilt the binding site away from the interface, potentially freeing the transporter or complex to move through the membrane. However, chains which are too long can also slow transport by inhibiting movement, and especially reorientation, within the phospholipid bilayer. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/21002 |
DOI: | 10.1002/chem.201504057 |
ISSN: | 0947-6539 |
Publisher Version: | 10.1002/chem.201504057 |
Appears in Collections: | CICECO - Artigos |
Files in This Item:
File | Description | Size | Format | |
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Tilting and Tumbling in Transmembrane Anion Carriers Activity Tuning through n-Alkyl Substitution_10.1002chem.201504057.pdf | 11.41 MB | Adobe PDF |
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