Chemical modification of conotoxins to improve stability and activity.
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.
Craik
David J
DJ
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Adams
David J
DJ
D000595:Amino Acid Sequence; D020916:Conotoxins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004220:Disulfides / Q000737:chemistry; D006207:Half-Life; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational
D020916:Conotoxins; D004220:Disulfides