Omega-Conotoxin GVIA mimetics that bind and inhibit neuronal Ca v2.2 ion channels

C Elisabet Tranberg; Aijun Yang; Irina Vetter; Jeffrey R McArthur; Jonathan Bayldon Baell; Richard J Lewis; Kellie Louise Tuck; Peter Duggan

doi:10.3390/md10102349

Omega-Conotoxin GVIA mimetics that bind and inhibit neuronal Ca v2.2 ion channels

C Elisabet Tranberg, Aijun Yang, Irina Vetter, Jeffrey R McArthur, Jonathan Bayldon Baell, Richard J Lewis, Kellie Louise Tuck, Peter Duggan

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19 Citations (Scopus)

Abstract

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 I?-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-I?-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 I?-conotoxin GVIA and found to be active in the 125I-I?- conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner.

Original language	English
Pages (from-to)	2349 - 2368
Number of pages	20
Journal	Marine Drugs
Volume	10
Issue number	10
DOIs	https://doi.org/10.3390/md10102349
Publication status	Published - 2012

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title = "Omega-Conotoxin GVIA mimetics that bind and inhibit neuronal Ca v2.2 ion channels",

abstract = "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 I?-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-I?-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 I?-conotoxin GVIA and found to be active in the 125I-I?- conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner.",

author = "Tranberg, {C Elisabet} and Aijun Yang and Irina Vetter and McArthur, {Jeffrey R} and Baell, {Jonathan Bayldon} and Lewis, {Richard J} and Tuck, {Kellie Louise} and Peter Duggan",

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T1 - Omega-Conotoxin GVIA mimetics that bind and inhibit neuronal Ca v2.2 ion channels

AU - Tranberg, C Elisabet

AU - Yang, Aijun

AU - Vetter, Irina

AU - McArthur, Jeffrey R

AU - Baell, Jonathan Bayldon

AU - Lewis, Richard J

AU - Tuck, Kellie Louise

AU - Duggan, Peter

PY - 2012

Y1 - 2012

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AB - 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 I?-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-I?-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 I?-conotoxin GVIA and found to be active in the 125I-I?- conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner.

UR - http://www.mdpi.com/1660-3397/10/10/2349

U2 - 10.3390/md10102349

DO - 10.3390/md10102349

M3 - Article

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SP - 2349

EP - 2368

JO - Marine Drugs

JF - Marine Drugs

IS - 10

ER -

Omega-Conotoxin GVIA mimetics that bind and inhibit neuronal Ca v2.2 ion channels

Abstract

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