Projects per year
Abstract
Transmembrane anion carriers (anionophores) have potential in biological research and medicine, provided high activities can be obtained. There is particular interest in treating cystic fibrosis (CF), a genetic illness caused by deficient anion transport. Previous work has found that anionophore designs featuring axial ureas on steroid and trans-decalin scaffolds can be especially effective. Here we show that replacement of ureas by thioureas yields substantial further enhancements. Six new bis-thioureas have been prepared and tested for Cl-/NO3 - exchange in 1-palmitoyl-2-oleoylphosphatidylcholine/cholesterol large unilamellar vesicles (LUVs). The bis-thioureas are typically >10 times more effective than the corresponding ureas and are sufficiently active that transport by molecules acting singly in LUVs is readily detected. The highest activity is shown by decalin 9, which features N-(3,5-bis(trifluoromethyl)phenyl)thioureido and octyl ester substituents. A single molecule of transporter 9 in a 200 nm vesicle promotes Cl-/NO3 - exchange with a half-life of 45 s and an absolute rate of 850 chloride anions per second. Weight-for-weight, this carrier is only slightly less effective than CFTR, the natural anion channel associated with CF. © 2014 American Chemical Society.
Original language | English |
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Pages (from-to) | 12507-12512 |
Number of pages | 6 |
Journal | Journal of the American Chemical Society |
Volume | 136 |
Issue number | 35 |
Early online date | 19 Aug 2014 |
DOIs | |
Publication status | Published - 3 Sept 2014 |
Keywords
- BIOLOGICAL APPLICATIONS
- RECEPTORS
- MEMBRANES
- ANIONOPHORES
- SELECTIVITY
- PRINCIPLE
- CHEMISTRY
- CONSTANTS
- CHANNEL
- ASSAY
Fingerprint
Dive into the research topics of 'Preorganized bis-thioureas as powerful anion carriers: Chloride transport by single molecules in large unilamellar vesicles'. Together they form a unique fingerprint.Projects
- 3 Finished
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3-month Core Capability for Chemistry Research
Crosby, J. (Principal Investigator)
1/01/13 → 1/04/13
Project: Research
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Synthetic Anionophores with Therapeutic Potential - a Coordinated Two-Centre Approach
Davis, A. P. (Principal Investigator)
10/09/12 → 9/03/16
Project: Research
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SYNTHETIC ANION CARRIERS FOR BIOMEDICAL APPLICATIONS
Davis, A. P. (Principal Investigator)
1/11/08 → 1/03/12
Project: Research
Profiles
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Professor Anthony P Davis
- School of Chemistry - Professor of Supramolecular Chemistry
Person: Academic