Two new classes of conopeptides inhibit the α1-adrenoceptor and noradrenaline transporter

@article{Sharpe2001TwoNC,
  title={Two new classes of conopeptides inhibit the $\alpha$1-adrenoceptor and noradrenaline transporter},
  author={Iain A. Sharpe and Jan Gehrmann and Marion L. Loughnan and Linda Thomas and Denise A. Adams and Annette R. Atkins and Elka Palant and David J. Craik and David John Adams and Paul F. Alewood and Richard James Lewis},
  journal={Nature Neuroscience},
  year={2001},
  volume={4},
  pages={902-907}
}
Cone snails use venom containing a cocktail of peptides ('conopeptides') to capture their prey. Many of these peptides also target mammalian receptors, often with exquisite selectivity. Here we report the discovery of two new classes of conopeptides. One class targets α1-adrenoceptors (ρ-TIA from the fish-hunting Conus tulipa), and the second class targets the neuronal noradrenaline transporter (χ-MrIA and χ-MrIB from the mollusk-hunting C. marmoreus). ρ-TIA and χ-MrIA selectively modulate… 
Toxins 'R' Us: more pharmacological tools from nature's superstore.
  • A. Harvey
  • Biology, Chemistry
    Trends in pharmacological sciences
  • 2002
Therapeutic potential of cone snail venom peptides (conopeptides).
TLDR
Several conopeptides reduce pain in animals models, with one in clinical development and one marketed (ω- conotoxin MVIIA or Prialt) for the treatment of severe pain.
Conus Venom Peptide Pharmacology
TLDR
The discovery of new bioactives using proteomic/transcriptomic approaches combined with high-throughput platforms and better defining conopeptide structure-activity relationships using relevant membrane protein crystal structures are expected to grow the already significant impact conopePTides have had as both research probes and leads to new therapies.
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TLDR
In this chapter, the marine cone snails and their venoms are introduced and the chemical diversity of conopeptides is described, along with the techniques used to unravel this diversity.
Identification and functional characterization of a novel α-conotoxin (EIIA) from Conus ermineus
TLDR
The mass spectrometric-based approaches which led to the discovery of a novel α-conotoxin targeting muscular nAChR from the venom of Conus ermineus are described and a clear discrimination between the two binding sites described for this receptor is revealed.
Conotoxins: Therapeutic Potential and Application
TLDR
The pharmacology and therapeutic rationale of those conotoxins with potential clinical application are surveyed, and the unique challenges that each will face in the course of their transition from venom component to human therapeutic are discussed.
Allosteric α1-Adrenoreceptor Antagonism by the Conopeptide ρ-TIA*
TLDR
The unique allosteric antagonism of ρ-TIA resulting from its interaction with receptor residues that constitute a binding site that is distinct from that of the classical competitive α1-adrenoreceptor antagonists may allow the development of inhibitors that are highly subtype selective.
Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications.
TLDR
This review discusses their gene superfamily classification, nomenclature, post-translational modification, structural framework, pharmacology and medical applications of the active conopeptides and aims to give an overview of their structure and therapeutic potential.
Selecting Potential Neuronal Drug Leads from Conotoxins of Various Venomous Marine Cone Snails in Bali, Indonesia
TLDR
Data is provided on pharmacological families of the conotoxins of 11 species of cone snails collected in Bali that possibly targeting neuronal tissues were α (alpha), ι (iota), κ (kappa), and ρ (rho), which shall target nicotinic acetylcholine receptors, voltage-gated Na channels, voltage -gated K channels, and α1-adrenoceptors, respectively.
Discovery and development of the χ-conopeptide class of analgesic peptides.
  • R. Lewis
  • Biology
    Toxicon : official journal of the International Society on Toxinology
  • 2012
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