Using synthetic small molecules to probe the structure and function of voltage-gated ion channels
Abstract/Contents
- Abstract
- Several methods of examining the structure and function of voltage-gated ion channels are described. The first part of this work involves synthetic small molecules based on the structure of (+)-saxitoxin, a marine neurotoxin. (+)-saxitoxin interacts with the pore of the voltage-gated sodium (NaV ) channel to prevent the passage of ions. A scaffold was designed to be modular, synthetically facile, and contain the functionality that had been implicated in the previous literature. Several members of this family of molecules were produced, and they were assayed for occlusion of sodium current (INa). The second part of this work examines the gating kinetics of voltage-gated potassium (KV) channels. 6-bromo-mercaptotryptamine (BrMT) is a marine neurotoxin that has been shown to alter the gating kinetics of KV channels. Specifically, BrMT affects the early, typically independent steps of KV gating by stabilizing the resting state of some number of the subunits. A family of small molecules was designed and synthesized that would examine the functional effects of different parts of the BrMT molecule. BrMT is a dimer containing three key functional groups: a halogenated indole, a pendant ethyl-amine, and a disulfide linker. Variance at all these positions was examined, and each had different effects. Notably, one of the variants, in which the disulfide linker was substituted for an oxy-bismethyl ether linker, affects KV gating in a different way from BrMT. Alternate models of gating in the presence of this novel analog are discussed.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Litchfield, Justin David | |
|---|---|---|
| Associated with | Stanford University, Department of Chemistry | |
| Primary advisor | Aldrich, Richard | |
| Primary advisor | Du Bois, Justin | |
| Thesis advisor | Aldrich, Richard | |
| Thesis advisor | Du Bois, Justin | |
| Thesis advisor | Brauman, J. I. (John I.) | |
| Advisor | Brauman, J. I. (John I.) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Justin David Litchfield. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph. D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Justin David Litchfield
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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