Tilting and Tumbling in Transmembrane Anion Carriers: Activity Tuning through n-Alkyl Substitution.

Autor: Edwards SJ; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK., Marques I; Departamento de Química, iBiMED and CICECO, Universidade de Aveiro, 3810-193, Aveiro, Portugal., Dias CM; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK., Tromans RA; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK., Lees NR; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK., Félix V; Departamento de Química, iBiMED and CICECO, Universidade de Aveiro, 3810-193, Aveiro, Portugal. Vitor.Felix@ua.pt., Valkenier H; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. Hennie.Valkenier@bristol.ac.uk., Davis AP; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. Anthony.Davis@bristol.ac.uk.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2016 Feb; Vol. 22 (6), pp. 2004-2011. Date of Electronic Publication: 2016 Jan 08.
DOI: 10.1002/chem.201504057
Abstrakt: 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.
(© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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