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Papers of the Week

Papers: 13 Mar 2021 - 19 Mar 2021

Animal Studies, Pharmacology/Drug Development

2021 Mar 16

J Med Chem

Alkyne-Bridged α-Conotoxin Vc1.1 Potently Reverses Mechanical Allodynia in Neuropathic Pain Models.


Belgi A, Burnley JV, MacRaild CA, Chhabra S, Elnahriry KA, Robinson SD, Gooding SG, Tae H-S, Bartels P, Sadeghi M, Zhao F-Y, Wei H, Spanswick D, Adams DJ, Norton RS, Robinson AJ
J Med Chem. 2021 Mar 16.
PMID: 33724033.


Several -derived venom peptides are promising lead compounds for the management of neuropathic pain, with α-conotoxins being of particular interest. Modification of the interlocked disulfide framework of α-conotoxin Vc1.1 has been achieved using on-resin alkyne metathesis. Although introduction of a metabolically stable alkyne motif significantly disrupts backbone topography, the structural modification generates a potent and selective GABA receptor agonist that inhibits Ca2.2 channels and exhibits dose-dependent reversal of mechanical allodynia in a behavioral rat model of neuropathic pain. The findings herein support the hypothesis that analgesia can be achieved via activation of GABARs expressed in dorsal root ganglion (DRG) sensory neurons.