The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1

J Biol Chem. 2006 Aug 11;281(32):23254-63. doi: 10.1074/jbc.M604550200. Epub 2006 Jun 5.


The alpha-conotoxin Vc1.1 is a small disulfide-bonded peptide currently in development as a treatment for neuropathic pain. This study describes the synthesis, determination of the disulfide connectivity, and the determination of the three-dimensional structure of Vc1.1 using NMR spectroscopy. Vc1.1 was shown to inhibit nicotine-evoked membrane currents in isolated bovine chromaffin cells in a concentration-dependent manner and preferentially targets peripheral nicotinic acetylcholine receptor (nAChR) subtypes over central subtypes. Specifically, Vc1.1 is selective for alpha3-containing nAChR subtypes. The three-dimensional structure of Vc1.1 comprises a small alpha-helix spanning residues Pro6 to Asp11 and is braced by the I-III, II-IV disulfide connectivity seen in other alpha-conotoxins. A comparison of the structure of Vc1.1 with other alpha-conotoxins, taken together with nAChR selectivity data, suggests that the conserved proline at position 6 is important for binding, whereas a number of residues in the C-terminal portion of the peptide contribute toward the selectivity. The structure reported here should open new opportunities for further development of Vc1.1 or analogues as analgesic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / cytology
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Chromaffin Cells / cytology
  • Chromaffin Cells / metabolism
  • Conotoxins / chemistry*
  • Conotoxins / metabolism
  • Disulfides / chemistry
  • Electrophysiology
  • Kinetics
  • Magnetic Resonance Spectroscopy / methods*
  • Models, Molecular
  • Molecular Sequence Data
  • Nicotine / pharmacology
  • Oocytes / metabolism
  • Oxygen / metabolism
  • Peptides / chemistry
  • Proline / chemistry
  • Protein Binding
  • Protein Folding
  • Xenopus


  • Conotoxins
  • Disulfides
  • Peptides
  • alpha-conotoxin Vc1.1
  • Nicotine
  • Proline
  • Oxygen

Associated data

  • PDB/2H8S