Chemical modification of conotoxins to improve stability and activity

ACS Chem Biol. 2007 Jul 20;2(7):457-68. doi: 10.1021/cb700091j.


Conotoxins are small disulfide-rich peptides from the venom of cone snails. Along with other conopeptides, they target a wide range of membrane receptors, ion channels, and transporters, and because of their high potency and selectivity for defined subtypes of these receptors, they have attracted a great deal of attention recently as leads in drug development. However, like most peptides, conopeptides potentially suffer from the disadvantages of poor absorption, poor stability, or short biological half-lives. Recently, various chemical approaches, including residue substitutions, backbone cyclization, and disulfide-bridge modification, have been reported to increase the stability of conopeptides. These manufactured interventions add to the array of post-translational modifications that occur naturally in conopeptides. They enhance the versatility of these peptides as tools in neuroscience and as drug leads.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Conotoxins / chemistry*
  • Conotoxins / pharmacokinetics
  • Conotoxins / pharmacology*
  • Disulfides / chemistry
  • Half-Life
  • Molecular Sequence Data
  • Protein Processing, Post-Translational


  • Conotoxins
  • Disulfides