Skip to main content

Conotoxin Venom Peptide Therapeutics

  • Chapter
Pharmaceutical Biotechnology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 655))

Abstract

Venom peptides offer enormous opportunity for the discovery of peptide drug leads. This review focusses on the potential of cone snails that have developed arrays of small peptides as part of highly evolved venoms used for prey capture and defence. Many of these peptides selectively modulate ion channels and transporters, making them a valuable source of new ligands for studying the role these targets play in normal and disease physiology. A number of these conopeptides reduce pain in animals models and several are now in preclinical and clinical development for the treatment of severe pain often associated with diseases such as cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lewis RJ, Garcia ML. Therapeutic potential of venom peptides. Nature Reviews Drug Discovery 2003; 2:790–802.

    Article  CAS  PubMed  Google Scholar 

  2. Lewis RJ, Nielsen KJ, Craik DJ et al. Novel ω-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem 2000; 275:35335–35344.

    Article  CAS  PubMed  Google Scholar 

  3. Malmberg AB, Yaksh TL. Effect of continuous intrathecal infusion of omega-conopeptides, N-type calcium-channel blockers, on behavior and antinociception in the formalin, and hot-plate tests in rats. Pain 1995; 60:83–90.

    Article  CAS  PubMed  Google Scholar 

  4. Smith M, Cabot PJ, Ross FB et al. The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices. Pain 2002; 96:119–127.

    Article  CAS  PubMed  Google Scholar 

  5. Nielsen K, Schroeder T, Lewis RJ. Structure-activity relationships of ω-conotoxins at N-type voltage-sensitive calcium channels. J Mol Recognition 2000; 13:55–70.

    Article  CAS  Google Scholar 

  6. Schroeder CI, Smythe ML, Lewis RJ. Development of small molecules that mimic the binding of ω-conotoxins at the N-type voltage-gated calcium channel. Molec Diversity 2004; 8:127–134.

    Article  CAS  Google Scholar 

  7. Wood JN, Boorman J. Voltage-gated sodium channel blockers; target validation and therapeutic potential. Curr Top Med Chem 2005; 5:529–537.

    Article  CAS  PubMed  Google Scholar 

  8. Ekberg J, Jayamanne A, Vaughan CW et al. μO-conotoxin MrVIB selectively blocks Na, 1.8 sensory neuron specific sodium channels and chronic pain without motor deficits. Proc Natl Acad Sci 2006; 103:17030–17035.

    Article  CAS  PubMed  Google Scholar 

  9. Nicke A, Wonnacott S, Lewis RJ. α-Conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes. Eur J Biochem 2004; 271:2305–2319.

    Article  CAS  PubMed  Google Scholar 

  10. Sandall DW, Satkunanathan N, Keays DA et al. A novel α-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo Biochemistry 2003; 42:6904–11.

    Article  CAS  PubMed  Google Scholar 

  11. Sharpe IA, Gehrmann J, Loughnan ML et al. Two new classes of conopeptides inhibit the α1-adrenoceptor and noradrenaline transporter. Nature Neurosci 2001; 4:902–907.

    Article  CAS  PubMed  Google Scholar 

  12. Nielsen CK, Lewis RJ, Alewood D et al. Anti-allodynic efficacy of the ξ-conopeptide, Xen2174, in rats with neuropathic pain. Pain 2005; 118:112–124.

    Article  CAS  PubMed  Google Scholar 

  13. Paczkowski FA, Sharpe IA, Dutertre S et al. ξ-Conopeptide and tricyclic anti-depressant interactions at the norepinephrine transporter define a new transporter model. J Biol Chem 2007; 282:17837–17844.

    Article  CAS  PubMed  Google Scholar 

  14. Malmberg AB, Gilbert H, McCabe RT et al. Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T. Pain 2003; 101:109–116.

    Article  CAS  PubMed  Google Scholar 

  15. Craig AG, Norberg T, Griffin D et al. Contulakin-G, an O-glycosylated invertebrate neurotensin. J Biol Chem 1999; 274:13752–9.

    Article  CAS  PubMed  Google Scholar 

  16. Allen JW, Hofer K, McCumber D et al. An assessment of the antinociceptive efficacy of intrathecal and epidural contulakin-G in rats and dogs. Anesth Analg 2007; 104:1505–13.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Lewis, R.J. (2009). Conotoxin Venom Peptide Therapeutics. In: Guzmán, C.A., Feuerstein, G.Z. (eds) Pharmaceutical Biotechnology. Advances in Experimental Medicine and Biology, vol 655. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1132-2_5

Download citation

Publish with us

Policies and ethics