ω-conotoxin GVIA mimetics that bind and inhibit neuronal Cav2.2 ion channels
Tranberg, C.E.; Yang, A.; Vetter, I.; McArthur, J.R.; Baell, J.B.; Lewis, R.J.; Tuck, K.L.; Duggan, P.J. (2012). ω-conotoxin GVIA mimetics that bind and inhibit neuronal Cav2.2 ion channels. Mar. Drugs 10(10): 2349-2368. https://dx.doi.org/10.3390/md10102349
In: Marine Drugs. Molecular Diversity Preservation International (MDPI): Basel. ISSN 1660-3397; e-ISSN 1660-3397, more
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| Keyword |
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| Author keywords |
Cav2.2; conotoxin; peptidomimetics; radioligand binding; Ca2+ fluorescence assay; patch clamp electrophysiology |
| Authors | | Top |
- Tranberg, C.E.
- Yang, A.
- Vetter, I., more
- McArthur, J.R.
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- Baell, J.B.
- Lewis, R.J.
- Tuck, K.L.
- Duggan, P.J.
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| Abstract |
The neuronal voltage-gated N-type calcium channel (Cav2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived ω-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-ω-conotoxin GVIA displacement assay, a fluorescence-based calcium response assay with SH-SY5Y neuroblastoma cells, and a whole-cell patch clamp electrophysiology assay with HEK293 cells stably expressing human Cav2.2 channels. A subset of compounds were active in all three assays. This is the first time that compounds designed to be mimics of ω-conotoxin GVIA and found to be active in the 125I-ω-conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner. |
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