Saxitoxin-derived probes for labeling voltage-gated sodium channels
Abstract/Contents
- Abstract
- Voltage-gated sodium channels (NaVs) are obligatory membrane proteins responsible for the initiation and propagation of bioelectricity in excitable cells. A desire to study channel trafficking and regulatory mechanisms inspires the development of molecular tools for labeling channels patterned after the bis-guanidinium neurotoxin, (+)-saxitoxin (STX). The synthesis and electrophysiological evaluation of a novel class of cysteine-reactive, trifunctional STX-maleimide conjugates are described herein. These probes covalently inhibit wild-type NaVs, and contain a fluorophore, affinity, or bioorthogonal tag for visualizing and/or isolating toxin-bound channels. STX-maleimide derivatives were also demonstrated to covalently inhibit cysteine mutant channels, enabling the development of an orthogonal ligand-receptor pair. In addition, the preparation and characterization of reversible fluorescent STX conjugates are also described, which display excellent potency against neuronal NaV subytpes. Such reagents therefore represent valuable imaging agents for the visualization of NaVs in cultured neurons.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Finkelstein, Darren Steven |
|---|---|
| Associated with | Stanford University, Department of Chemistry. |
| Primary advisor | Du Bois, Justin |
| Thesis advisor | Du Bois, Justin |
| Thesis advisor | Chen, James Kenneth |
| Thesis advisor | Wender, Paul A |
| Advisor | Chen, James Kenneth |
| Advisor | Wender, Paul A |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Darren Steven Finkelstein. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Darren Steven Finkelstein
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...