%0 Journal Article
%T ¦Ø-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Cav2.2 Ion Channels
%A Charlotte Elisabet Tranberg
%A Aijun Yang
%A Irina Vetter
%A Jeffrey R. McArthur
%A Jonathan B. Baell
%A Richard J. Lewis
%A Kellie L. Tuck
%A Peter J. Duggan
%J Marine Drugs
%D 2012
%I MDPI AG
%R 10.3390/md10102349
%X The neuronal voltage-gated N-type calcium channel (Ca v2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived ¦Ø-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-¦Ø-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 Ca v2.2 channels. A subset of compounds were active in all three assays. This is the first time that compounds designed to be mimics of ¦Ø-conotoxin GVIA and found to be active in the 125I-¦Ø-conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner.
%K Cav2.2
%K conotoxin
%K peptidomimetics
%K radioligand binding
%K Ca2+ fluorescence assay
%K patch clamp electrophysiology
%U http://www.mdpi.com/1660-3397/10/10/2349