Conotoxins: Characterization, Pharmacology, and Therapeutics

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

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 7777

Special Issue Editor

Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725, USA
Interests: conotoxins; Veratrum alkaloids; chemistry and bioactivity of natural products from marine and terrestrial sources; food and dairy chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Conotoxins have been studied extensively for use as therapeutic drugs to treat pain, neurological disorders, and a variety of common ailments. FDA approval of the drug Ziconotide in 2004 demonstrated the potential for conotoxins to be used in native form for the treatment of chronic pain. These small peptides selectively target biological receptors and exhibit some of the most intense responses observed from any natural product.

In this Special Issue, papers are sought that contribute to the wealth of information regarding conotoxin sequence, structure, and activity characterization, demonstrate bioactivity evaluation methods to assess conotoxin pharmacological response, and describe potential peptide candidates for therapeutic applications. Submissions are encouraged from groups that report native peptide discovery, synthetic peptide experimentation, and computationally designed conotoxin analogues. Modern strategies for evaluating conotoxin pharmacology and innovative systems for studying activity and receptor binding are anticipated.

Prof. Dr. Owen M. McDougal
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

  • conotoxin
  • structure activity relationship
  • nicotinic acetylcholine receptor
  • mutational analysis
  • positional scanning synthetic combinatorial libraries
  • bioactivity characterization
  • therapeutic applications

Published Papers (2 papers)

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14 pages, 1621 KiB  
Article
Qualitative Assay to Detect Dopamine Release by Ligand Action on Nicotinic Acetylcholine Receptors
by Leanna A. Marquart, Matthew W. Turner and Owen M. McDougal
Toxins 2019, 11(12), 682; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11120682 - 20 Nov 2019
Cited by 5 | Viewed by 3104
Abstract
A pheochromocytoma of the rat adrenal medulla derived (a.k.a. PC12) cell-based assay for dopamine measurement by luminescence detection was customized for the qualitative evaluation of agonists and antagonists of nicotinic acetylcholine receptors (nAChRs). The assay mechanism begins with ligand binding to transmembrane nAChRs, [...] Read more.
A pheochromocytoma of the rat adrenal medulla derived (a.k.a. PC12) cell-based assay for dopamine measurement by luminescence detection was customized for the qualitative evaluation of agonists and antagonists of nicotinic acetylcholine receptors (nAChRs). The assay mechanism begins with ligand binding to transmembrane nAChRs, altering ion flow into the cell and inducing dopamine release from the cell. Following release, dopamine is oxidized by monoamine oxidase generating hydrogen peroxide that catalyzes a chemiluminescence reaction involving luminol and horseradish peroxidase, thus producing a detectable response. Results are presented for the action of nAChR agonists (acetylcholine, nicotine, and cytisine), and antagonists (α-conotoxins (α-CTxs) MII, ImI, LvIA, and PeIA) that demonstrate a luminescence response correlating to the increase or decrease of dopamine release. A survey of cell growth and treatment conditions, including nerve growth factor, nicotine, ethanol, and temperature, led to optimal assay requirements to achieve maximal signal intensity and consistent response to ligand treatment. It was determined that PC12 cells treated with a combination of nerve growth factor and nicotine, and incubated at 37 °C, provided favorable results for a reduction in luminescence signal upon treatment of cells with α-CTxs. The PC12 assay is intended for use as a fast, efficient, and economic qualitative method to assess the bioactivity of molecules that act on nAChRs, in which testing of ligand–nAChR binding hypotheses and computational predictions can be validated. As a screening method for nAChR bioactivity, lead compounds can be assessed for their likelihood of exhibiting desired bioactivity prior to being subjected to more complex quantitative methods, such as electrophysiology or live animal studies. Full article
(This article belongs to the Special Issue Conotoxins: Characterization, Pharmacology, and Therapeutics)
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Review

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25 pages, 1381 KiB  
Review
α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia
by Adam C. Kennedy, Alessia Belgi, Benjamin W. Husselbee, David Spanswick, Raymond S. Norton and Andrea J. Robinson
Toxins 2020, 12(8), 505; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12080505 - 06 Aug 2020
Cited by 19 | Viewed by 4364
Abstract
Several analgesic α-conotoxins have been isolated from marine cone snails. Structural modification of native peptides has provided potent and selective analogues for two of its known biological targets—nicotinic acetylcholine and γ-aminobutyric acid (GABA) G protein-coupled (GABAB) receptors. Both of these molecular [...] Read more.
Several analgesic α-conotoxins have been isolated from marine cone snails. Structural modification of native peptides has provided potent and selective analogues for two of its known biological targets—nicotinic acetylcholine and γ-aminobutyric acid (GABA) G protein-coupled (GABAB) receptors. Both of these molecular targets are implicated in pain pathways. Despite their small size, an incomplete understanding of the structure-activity relationship of α-conotoxins at each of these targets has hampered the development of therapeutic leads. This review scrutinises the N-terminal domain of the α-conotoxin family of peptides, a region defined by an invariant disulfide bridge, a turn-inducing proline residue and multiple polar sidechain residues, and focusses on structural features that provide analgesia through inhibition of high-voltage-activated Ca2+ channels. Elucidating the bioactive conformation of this region of these peptides may hold the key to discovering potent drugs for the unmet management of debilitating chronic pain associated with a wide range of medical conditions. Full article
(This article belongs to the Special Issue Conotoxins: Characterization, Pharmacology, and Therapeutics)
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