Membrane transport activity of isophthalate amphiphiles
| dc.contributor.author | Knoy, Ryan Lee | en_US |
| dc.date.accessioned | 2024-08-14T18:31:47Z | |
| dc.date.available | 2024-08-14T18:31:47Z | |
| dc.date.copyright | 2000 | en_US |
| dc.date.issued | 2000 | |
| dc.degree.department | Department of Chemistry | |
| dc.degree.level | Master of Science M.Sc. | en |
| dc.description.abstract | This research addresses the issue of the minimum structural requirements to formcation conducting channels in lipid bilayers. A suite of fifteen alkoxy substituted isophthalates has been assessed. Two surveys were conducted to demonstrate cation channel formation: one in planar bilayers using the voltage-clamp technique and the second conducted in vesicle bilayers using a pH stat technique. In both techniques, membranes were formed from a mixture of 8: 1: 1 phosphatidylcholine, phosphatidic acid, and cholesterol. In the bilayer clamp experiment, membranes were formed between two aqueous compartments of IM alkali chloride salts (NaCl, KCI, CsCl). A transmembrane potential was applied and the transmembrane current was measured. Compounds were introduced as solutions in methanol or dimethyl sulphoxide and experiments were controlled to provide equivalent conditions for channel formation to all compounds. Only one active compound was uncovered from planar bilayer clamp experiments under the conditions of the survey. 5-(12-Tricosanoxy-)-isophthalic acid consistently induced step changes in conductance in the three alkali chlorides. The step-changes in conductance were characterized as behaving according to Ohm's law, with cation selectivity manifest as Cs+> K+ > Na+. A range of conductance values (15.4 pS to 16 pS for K+) was observed in some experiments, indicating flexibility in the active structure. This active isophthalate was used as a model for two new homologs, in order to probe the dependence of alkoxy length on cation channel formation. These two homo logs and the original suite of fifteen were examined in vesicles through the pH stat technique. The homologs synthesized were inactive in vesicles; however, two of the others were found to be active in vesicles. Using a modified voltage-clamp procedure, one of the isophthalates gave irregular current-time records and the other gave consistent, well-defined activity of typically short duration. For the isophthalate producing irregular current-time traces, the magnitude of the current observed is consistent with the vesicle results. Under the modified conditions, one of the synthesized homo logs (5-(-13-pentacosanoxy-) -isophthalic acid), also gave infrequent single channel openings. f-rom the seventeen compounds examined, channel forming activity was observed for four compounds. The research provides reasonable evidence that defined cation-channel forming structures can be formed from relatively small amphiphiles. | |
| dc.format.extent | 117 pages | |
| dc.identifier.uri | https://hdl.handle.net/1828/18467 | |
| dc.rights | Available to the World Wide Web | en_US |
| dc.title | Membrane transport activity of isophthalate amphiphiles | en_US |
| dc.type | Thesis | en_US |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- Knoy_Ryan_BSC_1998_1120889.pdf
- Size:
- 38.83 MB
- Format:
- Adobe Portable Document Format