Next Article in Journal
Botulinum Toxin for Central Neuropathic Pain
Previous Article in Journal
Monocentric Prospective Study into the Sustained Effect of Incobotulinumtoxin A (XEOMIN®) Botulinum Toxin in Chronic Refractory Migraine
Previous Article in Special Issue
Selective Closed-State Nav1.7 Blocker JZTX-34 Exhibits Analgesic Effects against Pain
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessArticle
Toxins 2018, 10(6), 222; https://doi.org/10.3390/toxins10060222

Synthesis, Structure and Biological Activity of CIA and CIB, Two α-Conotoxins from the Predation-Evoked Venom of Conus catus

1
Institut des Biomolécules Max Mousseron, UMR 5247, Université de Montpellier—CNRS, 34095 Montpellier, France
2
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia
3
Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, LMU Munich, Nußbaumstraße 26, 80336 Munich, Germany
4
Département de Physiologie, Institut de Génomique Fonctionnelle, CNRS/INSERM UMR 5203, Université de Montpellier, 34095 Montpellier, France
Present address: Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, Staudinger Weg 5, 55128 Mainz, Germany
*
Author to whom correspondence should be addressed.
Received: 27 April 2018 / Revised: 28 May 2018 / Accepted: 29 May 2018 / Published: 1 June 2018
(This article belongs to the Special Issue Toxins and Ion Channels)
Full-Text   |   PDF [2186 KB, uploaded 1 June 2018]   |  

Abstract

Cone snails produce a fast-acting and often paralyzing venom that is usually injected into their prey or predator through a hypodermic needle-like modified radula tooth. Many diverse compounds are found in their venom including small molecules, peptides and enzymes. However, peptidic toxins called conotoxins (10–40 residues and 2–4 disulfide bonds) largely dominate these cocktails. These disulfide rich toxins are very valuable pharmacological tools for investigating the function of ions channels, G-protein coupled receptors, transporters and enzymes. Here, we report on the synthesis, structure determination and biological activities of two α-conotoxins, CIA and CIB, found in the predatory venom of the piscivorous species Conus catus. CIA is a typical 3/5 α-conotoxin that blocks the rat muscle type nAChR with an IC50 of 5.7 nM. Interestingly, CIA also inhibits the neuronal rat nAChR subtype α3β2 with an IC50 of 2.06 μM. CIB is a 4/7 α-conotoxin that blocks rat neuronal nAChR subtypes, including α3β2 (IC50 = 128.9 nM) and α7 (IC50 = 1.51 μM). High resolution NMR structures revealed typical α-conotoxin folds for both peptides. We also investigated the in vivo effects of these toxins on fish, since both peptides were identified in the predatory venom of C. catus. Consistent with their pharmacology, CIA was highly paralytic to zebrafish (ED50 = 110 μg/kg), whereas CIB did not affect the mobility of the fish. In conclusion, CIA likely participates in prey capture through muscle paralysis, while the putative ecological role of CIB remains to be elucidated. View Full-Text
Keywords: conotoxins; Conus catus; electrophysiology; in vivo; nicotinic receptors; structure; synthesis conotoxins; Conus catus; electrophysiology; in vivo; nicotinic receptors; structure; synthesis
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Giribaldi, J.; Wilson, D.; Nicke, A.; El Hamdaoui, Y.; Laconde, G.; Faucherre, A.; Moha Ou Maati, H.; Daly, N.L.; Enjalbal, C.; Dutertre, S. Synthesis, Structure and Biological Activity of CIA and CIB, Two α-Conotoxins from the Predation-Evoked Venom of Conus catus. Toxins 2018, 10, 222.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top