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Mar. Drugs 2012, 10(10), 2349-2368; doi:10.3390/md10102349
Article

ω-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Cav2.2 Ion Channels

1,†
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Received: 12 September 2012; in revised form: 10 October 2012 / Accepted: 12 October 2012 / Published: 22 October 2012
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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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.
Keywords: Cav2.2; conotoxin; peptidomimetics; radioligand binding; Ca2+ fluorescence assay; patch clamp electrophysiology Cav2.2; conotoxin; peptidomimetics; radioligand binding; Ca2+ fluorescence assay; patch clamp electrophysiology
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Tranberg, C.E.; Yang, A.; Vetter, I.; McArthur, J.R.; Baell, J.B.; Lewis, R.J.; Tuck, K.L.; Duggan, P.J. ω-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Cav2.2 Ion Channels. Mar. Drugs 2012, 10, 2349-2368.

AMA Style

Tranberg CE, Yang A, Vetter I, McArthur JR, Baell JB, Lewis RJ, Tuck KL, Duggan PJ. ω-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Cav2.2 Ion Channels. Marine Drugs. 2012; 10(10):2349-2368.

Chicago/Turabian Style

Tranberg, Charlotte Elisabet; Yang, Aijun; Vetter, Irina; McArthur, Jeffrey R.; Baell, Jonathan B.; Lewis, Richard J.; Tuck, Kellie L.; Duggan, Peter J. 2012. "ω-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Cav2.2 Ion Channels." Mar. Drugs 10, no. 10: 2349-2368.


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