Salk Institute and University of Utah file patent US5969096: Conotoxin peptides

A paralytic peptide, ψ-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of α-bungarotoxin, a competitive nAChR antagonist. Thus, ψ-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure:  HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the α- or the αA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the μ-conotoxins (which are Na⁺ channel blockers).

— Biochemistry article

Substantially pure conotoxin peptides are provided which inhibit synaptic transmissions at the neuromuscular junctions and which are useful both in vivo and in assays because they specifically target particular skeletal nAChRs to the exclusion of neuronal nAChRs. The peptides are of such length that they can be made by chemical synthesis, and the preferred peptides have formula: H-His-4Hyp-4Hyp-Cys-Cys-Leu-Tyr-Gly-Lys-Cys-Arg-Arg-Tyr-4Hyp-Gly-Cys-Ser-S er-Ala-Ser-Cys-Cys-Gln-Xaa.sub.24 -NH.sub.2 wherein Xaa.sub.24 is Arg or Gly.

⋮

This invention was made with Government support under Grant Nos. GM-48677, GM-22737 and AM-26741, awarded by the National Institutes of Health.  The Government has certain rights in this invention.

— United States Patent 5.969.096: Conotoxin peptides

Sources:

• 
  October 19, 1999. Ki-Joon Shon, William R. Gray, John Dykert, Doju Yoshikami, Maren Watkins, David R. Hillyard, Jean E. F. Rivier, and Baldomero M. Olivera. Conotoxin peptides. 5969096, filed June 26, 1998, and issued October 19, 1999.
  https://patents.google.com/patent/US5969096,
  https://patents.justia.com/patent/5969096.
  Patent.
  Local copy.
• 
  August 1, 1997. Ki-Joon Shon, Michelle Grilley, Richard Jacobsen, G. Edward Cartier, Chris Hopkins, William R. Gray, Maren Watkins, David R. Hillyard, Jean Rivier, Josep Torres, Doju Yoshikami, and Baldomero M. Olivera. “A Noncompetitive Peptide Inhibitor of the Nicotinic Acetylcholine Receptor from Conus Purpurascens Venom.” Biochemistry 36 (31): 9581–87.
  https://doi.org/10.1021/bi970235w.
  Research Journal.

Related:

• 
  “Bungarotoxin.” In Wikipedia.
  https://en.wikipedia.org/w/index.php?title=Bungarotoxin.
  Reference.
• 
  “Conotoxin.” In Wikipedia.
  https://en.wikipedia.org/w/index.php?title=Conotoxin.
  Reference.
• 
  “Conus Purpurascens.” In Wikipedia.
  https://en.wikipedia.org/w/index.php?title=Conus_purpurascens.
  Reference.
• 
  “Nicotinic Acetylcholine Receptor.” In Wikipedia.
  https://en.wikipedia.org/w/index.php?title=Nicotinic_acetylcholine_receptor.
  Reference.
• 
  “Sodium Channel Blocker.” In Wikipedia.
  https://en.wikipedia.org/w/index.php?title=Sodium_channel_blocker.
  Reference.

See also, on this site:

• • “Dr. Ardis Was WRONG”