7KNN

Solution structure of the alpha-conotoxin analogue [2-8]-alkyne Vc1.1

Summary for 7KNN

• Entry DOI: 10.2210/pdb7knn/pdb
• NMR Information: BMRB: 30811
• Descriptor: Alpha-conotoxin Vc1a (1 entity in total)
• Functional Keywords: conotoxin dicarba, toxin
• Biological source: Conus victoriae (Queen Victoria cone)
• Total number of polymer chains: 1
• Total formula weight: 1777.93

Authors

MacRaild, C.A.,Robinson, S.D.,Chhabra, S.,Norton, R.S. (deposition date: 2020-11-05, release date: 2021-09-15, Last modification date: 2023-11-15)

Primary citation

Belgi, A.,Burnley, J.V.,MacRaild, C.A.,Chhabra, S.,Elnahriry, K.A.,Robinson, S.D.,Gooding, S.G.,Tae, H.S.,Bartels, P.,Sadeghi, M.,Zhao, F.Y.,Wei, H.,Spanswick, D.,Adams, D.J.,Norton, R.S.,Robinson, A.J.
Alkyne-Bridged alpha-Conotoxin Vc1.1 Potently Reverses Mechanical Allodynia in Neuropathic Pain Models.
J.Med.Chem., 64:3222-3233, 2021

PubMed Abstract: 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.

PubMed: 33724033
DOI: 10.1021/acs.jmedchem.0c02151

Experimental method

SOLUTION NMR