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Marine Drugs
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Marine Toxins from Venom: Potential Pharmaceutical and Medicinal Application Exploration
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Marine Toxins from Venom: Potential Pharmaceutical and Medicinal Application Exploration

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (29 February 2020) | Viewed by 12093

Special Issue Editor

Dr. David Wilson

E-Mail Website
Guest Editor
Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), Australian Institute of Tropical Health and Medicine (AITHM), James Cook University, McGregor Road, Smithfield, Cairns 4878, Australia
Interests: venomous animals; NMR spectroscopy; drug discovery and development

Special Issue Information

Dear Colleagues,

Bioactive molecules continue to be of increasing interest as potential therapeutics and therapeutic leads. Venoms are an extensive natural source of highly potent and specific bioactive compounds, in particular peptides and proteins. Venomous marine organisms are no exception and, although they have provided the source for the clinically available peptide drug for the treatment of chronic pain, Prialt®, the diverse resource they offer remains largely uncharted.

The Special Issue of Marine Drugs titled “Marine Toxins from Venom: Potential Pharmaceutical and Medicinal Application Exploration” aims to explore the current state and future perspectives of bioactive molecule discovery from the venom of marine organisms and their potential in pharmaceutical, pharmacological tool, and medicinal applications. Original manuscripts and reviews of the current literature related to the discovery, characterization, biological target modulation, and clinical development of bioactive molecules possessing therapeutic potential isolated from the venom of marine organism are encouraged.  

Dr. David Wilson
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 single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs 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 2900 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

  • Toxins
  • Peptides
  • Venom
  • Medicinal application
  • Pharmaceutical potential
  • Proteins
  • Marine natural compounds
  • Neurotoxins

Published Papers (3 papers)

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Research

14 pages, 2604 KiB  
Article
Synthesis, Pharmacological and Structural Characterization of Novel Conopressins from Conus miliaris
by Julien Giribaldi, Lotten Ragnarsson, Tom Pujante, Christine Enjalbal, David Wilson, Norelle L. Daly, Richard J. Lewis and Sebastien Dutertre
Mar. Drugs 2020, 18(3), 150; https://doi.org/10.3390/md18030150 - 06 Mar 2020
Cited by 10 | Viewed by 3098
Abstract
Cone snails produce a fast-acting and often paralyzing venom, largely dominated by disulfide-rich conotoxins targeting ion channels. Although disulfide-poor conopeptides are usually minor components of cone snail venoms, their ability to target key membrane receptors such as GPCRs make them highly valuable as [...] Read more.
Cone snails produce a fast-acting and often paralyzing venom, largely dominated by disulfide-rich conotoxins targeting ion channels. Although disulfide-poor conopeptides are usually minor components of cone snail venoms, their ability to target key membrane receptors such as GPCRs make them highly valuable as drug lead compounds. From the venom gland transcriptome of Conus miliaris, we report here on the discovery and characterization of two conopressins, which are nonapeptide ligands of the vasopressin/oxytocin receptor family. These novel sequence variants show unusual features, including a charge inversion at the critical position 8, with an aspartate instead of a highly conserved lysine or arginine residue. Both the amidated and acid C-terminal analogues were synthesized, followed by pharmacological characterization on human and zebrafish receptors and structural investigation by NMR. Whereas conopressin-M1 showed weak and only partial agonist activity at hV1bR (amidated form only) and ZFV1a1R (both amidated and acid form), both conopressin-M2 analogues acted as full agonists at the ZFV2 receptor with low micromolar affinity. Together with the NMR structures of amidated conopressins-M1, -M2 and -G, this study provides novel structure-activity relationship information that may help in the design of more selective ligands. Full article
(This article belongs to the Special Issue Marine Toxins from Venom: Potential Pharmaceutical and Medicinal Application Exploration)
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16 pages, 3760 KiB  
Article
Structure-Function Elucidation of a New α-Conotoxin, MilIA, from Conus milneedwardsi
by Steve Peigneur, Prabha Devi, Andrea Seldeslachts, Samuthirapandian Ravichandran, Loïc Quinton and Jan Tytgat
Mar. Drugs 2019, 17(9), 535; https://doi.org/10.3390/md17090535 - 16 Sep 2019
Cited by 12 | Viewed by 4302
Abstract
The a-Conotoxins are peptide toxins that are found in the venom of marine cone snails and they are potent antagonists of various subtypes of nicotinic acetylcholine receptors (nAChRs). Because nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, [...] Read more.
The a-Conotoxins are peptide toxins that are found in the venom of marine cone snails and they are potent antagonists of various subtypes of nicotinic acetylcholine receptors (nAChRs). Because nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, nAChR dysfunctions have been implicated in a variety of severe pathologies. We describe the isolation and characterization of α-conotoxin MilIA, the first conopeptide from the venom of Conus milneedwardsi. The peptide was characterized by electrophysiological screening against several types of cloned nAChRs that were expressed in Xenopus laevis oocytes. MilIA, which is a member of the α3/5 family, is an antagonist of muscle type nAChRs with a high selectivity for muscle versus neuronal subtype nAChRs. Several analogues were designed and investigated for their activity in order to determine the key epitopes of MilIA. Native MilIA and analogues both showed activity at the fetal muscle type nAChR. Two single mutations (Met9 and Asn10) allowed for MilIA to strongly discriminate between the two types of muscle nAChRs. Moreover, one analogue, MilIA [∆1,M2R, M9G, N10K, H11K], displayed a remarkable enhanced potency when compared to native peptide. The key residues that are responsible for switching between muscle and neuronal nAChRs preference were elucidated. Interestingly, the same analogue showed a preference for α9α10 nAChRs among the neuronal types. Full article
(This article belongs to the Special Issue Marine Toxins from Venom: Potential Pharmaceutical and Medicinal Application Exploration)
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13 pages, 2333 KiB  
Article
The α9α10 Nicotinic Acetylcholine Receptor Antagonist αO-Conotoxin GeXIVA[1,2] Alleviates and Reverses Chemotherapy-Induced Neuropathic Pain
by Huanbai Wang, Xiaodan Li, Dongting Zhangsun, Gang Yu, Ruibin Su and Sulan Luo
Mar. Drugs 2019, 17(5), 265; https://doi.org/10.3390/md17050265 - 05 May 2019
Cited by 39 | Viewed by 4180
Abstract
Oxaliplatin is a third-generation platinum drug and is widely used as a first-line therapy for the treatment of colorectal cancer (CRC). However, a large number of patients receiving oxaliplatin develop dose-limiting painful neuropathy. Here, we report that αO-conotoxin GeXIVA[1,2], a highly potent and [...] Read more.
Oxaliplatin is a third-generation platinum drug and is widely used as a first-line therapy for the treatment of colorectal cancer (CRC). However, a large number of patients receiving oxaliplatin develop dose-limiting painful neuropathy. Here, we report that αO-conotoxin GeXIVA[1,2], a highly potent and selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR) subtype, can relieve and reverse oxaliplatin-induced mechanical and cold allodynia after single and repeated intramuscular (IM) injections in rats. Treatments were started at 4 days post oxaliplatin injection when neuropathic pain emerged and continued for 8 and 16 days. Cold score and mechanical paw withdrawal threshold (PWT) were detected by the acetone test and von Frey test respectively. GeXIVA[1,2] significantly relieved mechanical and cold allodynia in oxaliplatin-treated rats after a single injection. After repeated treatments, GeXIVA[1,2] produced a cumulative analgesic effect without tolerance and promoted recovery from neuropathic pain. Moreover, the long lasting analgesic effect of GeXIVA[1,2] on mechanical allodynia continued until day 10 after the termination of the 16-day repeated treatment procedure. On the contrary, GeXIVA[1,2] did not affect acute mechanical and thermal pain behaviors in normal rats after repeated injections detected by the von Frey test and tail flick test. GeXIVA[1,2] had no influence on rat hind limb grip strength and body weight after repeated treatments. These results indicate that αO-conotoxin GeXIVA[1,2] could provide a novel strategy to treat chemotherapy-induced neuropathic pain. Full article
(This article belongs to the Special Issue Marine Toxins from Venom: Potential Pharmaceutical and Medicinal Application Exploration)
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