Conotoxins: Evolution, Classifications and Targets

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Marine and Freshwater Toxins".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4321

Special Issue Editor


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Guest Editor
Laboratory of Marine Neuropharmacology, Department of Cellular and Molecular Neurobiology, National Autonomous University of Mexico, Queretaro 76230, Mexico
Interests: peptides; proteins; toxins; cone snails; conopeptides; conotoxins; receptors; ion channels; nAChR

Special Issue Information

Dear Colleagues,

Cone snails are marine hunters that produce venoms mainly for capturing prey and self-defense. The major components of these venoms are peptidic compounds, named conotoxins or conopeptides. In general, conotoxins bind to their molecular targets (predominantly distinct receptors, and ligand- and voltage-gated ion channels) with high affinity and selectivity. This feature has allowed the application of varied conotoxins as molecular probes for diverse studies of ion channels and receptors, and of ω-conotoxin MVIIA (blocker of N-type calcium channels) as a medicine for chronic pain.

Diverse evidence indicates that less than 10% of the existing conotoxins have been uncovered, and that for less than 1% of them, one or more molecular target has been identified. Fortunately, continuing advances in proteomics and transcriptomics are constantly revealing plethoras of novel sequences, both for toxins and their precursors; however, both their pharmacological targets and their genetic origins are unknown. Therefore, I am pleased to invite you to submit articles to this Special Issue, “Conotoxins: Evolution, Classifications and Targets”.

This Special Issue aims to collect works that provide updates on several current central topics in the field of conotoxin research. Original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: the evolution, pharmacological and genetic classification of conotoxins and their precursors; and the prediction of molecular targets. Reports on omics of cone snail venoms, engineering of conopeptides and evaluation of their activities, identification and characterization of novel conotoxins, and synthesis of mimetics with improved properties are also appreciated.

Dr. Manuel B. Aguilar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cone snails
  • peptides
  • conopeptides
  • conotoxins
  • precursors
  • disulfide bonds
  • evolution
  • molecular targets
  • gene superfamilies
  • pharmacological families

Published Papers (3 papers)

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Research

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17 pages, 2152 KiB  
Article
Conotoxin Prediction: New Features to Increase Prediction Accuracy
by Lyman K. Monroe, Duc P. Truong, Jacob C. Miner, Samantha H. Adikari, Zachary J. Sasiene, Paul W. Fenimore, Boian Alexandrov, Robert F. Williams and Hau B. Nguyen
Toxins 2023, 15(11), 641; https://doi.org/10.3390/toxins15110641 - 03 Nov 2023
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Abstract
Conotoxins are toxic, disulfide-bond-rich peptides from cone snail venom that target a wide range of receptors and ion channels with multiple pathophysiological effects. Conotoxins have extraordinary potential for medical therapeutics that include cancer, microbial infections, epilepsy, autoimmune diseases, neurological conditions, and cardiovascular disorders. [...] Read more.
Conotoxins are toxic, disulfide-bond-rich peptides from cone snail venom that target a wide range of receptors and ion channels with multiple pathophysiological effects. Conotoxins have extraordinary potential for medical therapeutics that include cancer, microbial infections, epilepsy, autoimmune diseases, neurological conditions, and cardiovascular disorders. Despite the potential for these compounds in novel therapeutic treatment development, the process of identifying and characterizing the toxicities of conotoxins is difficult, costly, and time-consuming. This challenge requires a series of diverse, complex, and labor-intensive biological, toxicological, and analytical techniques for effective characterization. While recent attempts, using machine learning based solely on primary amino acid sequences to predict biological toxins (e.g., conotoxins and animal venoms), have improved toxin identification, these methods are limited due to peptide conformational flexibility and the high frequency of cysteines present in toxin sequences. This results in an enumerable set of disulfide-bridged foldamers with different conformations of the same primary amino acid sequence that affect function and toxicity levels. Consequently, a given peptide may be toxic when its cysteine residues form a particular disulfide-bond pattern, while alternative bonding patterns (isoforms) or its reduced form (free cysteines with no disulfide bridges) may have little or no toxicological effects. Similarly, the same disulfide-bond pattern may be possible for other peptide sequences and result in different conformations that all exhibit varying toxicities to the same receptor or to different receptors. We present here new features, when combined with primary sequence features to train machine learning algorithms to predict conotoxins, that significantly increase prediction accuracy. Full article
(This article belongs to the Special Issue Conotoxins: Evolution, Classifications and Targets)
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Review

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17 pages, 2798 KiB  
Review
Voltage-Gated Sodium Channel Inhibition by µ-Conotoxins
by Kirsten L. McMahon, Irina Vetter and Christina I. Schroeder
Toxins 2024, 16(1), 55; https://doi.org/10.3390/toxins16010055 - 18 Jan 2024
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Abstract
µ-Conotoxins are small, potent pore-blocker inhibitors of voltage-gated sodium (NaV) channels, which have been identified as pharmacological probes and putative leads for analgesic development. A limiting factor in their therapeutic development has been their promiscuity for different NaV channel subtypes, [...] Read more.
µ-Conotoxins are small, potent pore-blocker inhibitors of voltage-gated sodium (NaV) channels, which have been identified as pharmacological probes and putative leads for analgesic development. A limiting factor in their therapeutic development has been their promiscuity for different NaV channel subtypes, which can lead to undesirable side-effects. This review will focus on four areas of µ-conotoxin research: (1) mapping the interactions of µ-conotoxins with different NaV channel subtypes, (2) µ-conotoxin structure–activity relationship studies, (3) observed species selectivity of µ-conotoxins and (4) the effects of µ-conotoxin disulfide connectivity on activity. Our aim is to provide a clear overview of the current status of µ-conotoxin research. Full article
(This article belongs to the Special Issue Conotoxins: Evolution, Classifications and Targets)
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14 pages, 4214 KiB  
Review
Diversity and Evolutionary Analysis of Venom Insulin Derived from Cone Snails
by Qiqi Guo, Meiling Huang, Ming Li, Jiao Chen, Shuanghuai Cheng, Linlin Ma and Bingmiao Gao
Toxins 2024, 16(1), 34; https://doi.org/10.3390/toxins16010034 - 09 Jan 2024
Cited by 1 | Viewed by 1308
Abstract
Cone snails possess a diverse array of novel peptide toxins, which selectively target ion channels and receptors in the nervous and cardiovascular systems. These numerous novel peptide toxins are a valuable resource for future marine drug development. In this review, we compared and [...] Read more.
Cone snails possess a diverse array of novel peptide toxins, which selectively target ion channels and receptors in the nervous and cardiovascular systems. These numerous novel peptide toxins are a valuable resource for future marine drug development. In this review, we compared and analyzed the sequence diversity, three-dimensional structural variations, and evolutionary aspects of venom insulin derived from different cone snail species. The comparative analysis reveals that there are significant variations in the sequences and three-dimensional structures of venom insulins from cone snails with different feeding habits. Notably, the venom insulin of some piscivorous cone snails exhibits a greater similarity to humans and zebrafish insulins. It is important to emphasize that these venom insulins play a crucial role in the predatory strategies of these cone snails. Furthermore, a phylogenetic tree was constructed to trace the lineage of venom insulin sequences, shedding light on the evolutionary interconnections among cone snails with diverse diets. Full article
(This article belongs to the Special Issue Conotoxins: Evolution, Classifications and Targets)
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