Chloride Transport through Supramolecular Barrel-Rosette Ion Channels: Lipophilic Control and Apoptosis-Inducing Activity
| Autor: | Arnab Mukherjee, Mayurika Lahiri, Pinaki Talukdar, Tanmoy Saha, Amitosh Gautam |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Cell Survival Lipid Bilayers Inorganic chemistry Molecular Conformation Supramolecular chemistry Apoptosis 010402 general chemistry 01 natural sciences Biochemistry Chloride Ion Channels Catalysis Ion chemistry.chemical_compound Colloid and Surface Chemistry Chlorides Cell Line Tumor medicine Humans Molecule Lipid bilayer Ion channel Ion Transport 010405 organic chemistry Chemistry Benzene General Chemistry 0104 chemical sciences Membrane Monomer Biophysics Hydrophobic and Hydrophilic Interactions medicine.drug |
| Zdroj: | Journal of the American Chemical Society. 138:16443-16451 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.6b10379 |
| Popis: | Despite the great interest in artificial ion channel design, only a small number of channel-forming molecules are currently available for addressing challenging problems, particularly in the biological systems. Recent advances in chloride-mediated cell death, aided by synthetic ion carriers, encouraged us to develop chloride selective supramolecular ion channels. The present work describes vicinal diols, tethered to a rigid 1,3-diethynylbenzene core, as pivotal moieties for the barrel-rosette ion channel formation, and the activity of such channels was tuned by controlling the lipophilicity of designed monomers. Selective transport of chloride ions via an antiport mechanism and channel formation in the lipid bilayer membranes were confirmed for the most active molecule. A theoretical model of the supramolecular barrel-rosette, favored by a network of intermolecular hydrogen bonding, has been proposed. The artificial ion-channel-mediated transport of chloride into cells and subsequent disruption of cellular ionic homeostasis were evident. Perturbation of chloride homeostasis in cells instigates cell death by inducing the caspase-mediated intrinsic pathway of apoptosis. |
| Databáze: | OpenAIRE |
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