Tilting and Tumbling in Transmembrane Anion Carriers: Activity Tuning through n-Alkyl Substitution
| Autor: | Vítor Félix, Sophie J. Edwards, Igor Marques, Christopher M. Dias, Robert A. Tromans, Anthony P. Davis, Nicholas R. Lees, Hennie Valkenier |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
EXTRACTION
anion transport MOLECULAR-DYNAMICS SIMULATIONS Stereochemistry Substituent Supramolecular chemistry 010402 general chemistry 01 natural sciences Chloride Supramolecular Chemistry Catalysis supramolecular chemistry BCS and TECS CDTs Molecular dynamics chemistry.chemical_compound ANIONOPHORES medicine lipophilicity Lipid bilayer Alkyl chemistry.chemical_classification Full Paper 010405 organic chemistry CHLORIDE TRANSPORT Organic Chemistry Transporter General Chemistry Full Papers Sciences bio-médicales et agricoles molecular dynamics 0104 chemical sciences RECEPTORS Membrane chemistry membranes FORCE-FIELD PRINCIPLE AMBER medicine.drug |
| Zdroj: | Chemistry, 22 (6 Chemistry (Weinheim an Der Bergstrasse, Germany) Edwards, S J, Marques, I, Dias, C M, Tromans, R A, Lees, N R, Félix, V, Valkenier, H & Davis, A P 2016, ' Tilting and Tumbling in Transmembrane Anion Carriers : Activity Tuning through n-Alkyl Substitution ', Chemistry-A European Journal, vol. 22, no. 6, pp. 2004-2011 . https://doi.org/10.1002/chem.201504057 Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| DOI: | 10.1002/chem.201504057 |
| Popis: | 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 C0 to C10 in two-carbon steps. Activities increase then decrease as the chain length grows, peaking quite sharply at C6 .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. FLWIN info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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