Characterization of an α 4/7-Conotoxin LvIF from Conus lividus That Selectively Blocks α3β2 Nicotinic Acetylcholine Receptor

Guo, Man; Yu, Jinpeng; Zhu, Xiaopeng; Zhangsun, Dongting; Luo, Sulan

doi:10.3390/md19070398

Cited by 7 publications

(9 citation statements)

References 56 publications

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“…658 α4/7-Conotoxin LvIF, a 16-residue synthesised peptide based upon genomic DNA clone data derived from C. lividis also exhibits potent inhibition of rα3β2 and rα6/α3β2β3 nAChR's. 659 The 17-residue peptide α4/7-conotoxin Lv1d ( C. lividis ) demonstrates in vivo analgesic effects. 660 A crystal structure of α4/7-conotoxin OmIA ( C. omaria ) with Lymnae stagnalis acetylcholine binding protein, at 2.47 Å resolution, has identified principal interactions between His5 and Ala7 of the conotoxin with C-loop residues Tyr185–Tyr192 and the conotoxin disulfide and Cys188–Cys189.…”

Section: Molluscsmentioning

confidence: 99%

Marine natural products

et al. 2023

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Section: Molluscsmentioning

confidence: 99%

Marine natural products

et al. 2023

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“…The same ability was revealed for synthetic Mr1.7 [ 117 ], derived from the C. marmoreus venom duct cDNA library [ 118 ] ( Table 2 ). Highly selective among the discovered α4/7-conotoxins were TxIB towards the α6/α3β2β3 receptor subtype [ 119 ], LvIA and Lt1.3 towards the α3β2 nAChR [ 120 , 121 ], and LvIF and Bt1.8 with high nanomolar affinity for α3β2 and α6/α3β2β3 subtypes [ 122 , 123 ], while α-conotoxins Lo1a and BnIA acted on the α7 nAChR (although with micromolar affinity) [ 124 , 125 ] ( Table 2 ). The latter, isolated from the C. bandanus venom, has the same sequence as α-conotoxin Mr1.1, previously identified from the cDNA library of C. marmoreus [ 126 ].…”

Section: Marine Origin Peptides Targeting Nachrsmentioning

confidence: 99%

Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications

et al. 2022

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The purpose of our review is to briefly show what different compounds of marine origin, from low molecular weight ones to peptides and proteins, offer for understanding the structure and mechanism of action of nicotinic acetylcholine receptors (nAChRs) and for finding novel drugs to combat the diseases where nAChRs may be involved. The importance of the mentioned classes of ligands has changed with time; a protein from the marine snake venom was the first excellent tool to characterize the muscle-type nAChRs from the electric ray, while at present, muscle and α7 receptors are labeled with the radioactive or fluorescent derivatives prepared from α-bungarotoxin isolated from the many-banded krait. The most sophisticated instruments to distinguish muscle from neuronal nAChRs, and especially distinct subtypes within the latter, are α-conotoxins. Such information is crucial for fundamental studies on the nAChR revealing the properties of their orthosteric and allosteric binding sites and mechanisms of the channel opening and closure. Similar data are provided by low-molecular weight compounds of marine origin, but here the main purpose is drug design. In our review we tried to show what has been obtained in the last decade when the listed classes of compounds were used in the nAChR research, applying computer modeling, synthetic analogues and receptor mutants, X-ray and electron-microscopy analyses of complexes with the nAChRs, and their models which are acetylcholine-binding proteins and heterologously-expressed ligand-binding domains.

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“…Acetylcholine receptors (AChRs) are widely expressed in the nervous systems, playing critical roles in various physiological processes. nAChRs are associated with various neurological diseases, such as Parkinson's disease, Alzheimer's disease, neuralgia and epilepsy [66]. According to pharmacological activities, AChRs are classified into nicotinic (nAChR) and muscarinic (mAChR) types.…”

Section: Structural and Functional Studies Of Conotoxins With Their R...mentioning

confidence: 99%

“…On the other hand, GeXIVA is in the preclinical stage as an analgesic for the neuralgia treatment, indicating that α9α10 nAChR blockers have a good prospect for the development of analgesia [71]. Other prominent compound target at nAChRs includes recently discovered octaoligoarginine R8, α-conotoxins RgIA and previously isolated LvIA and LvIF from Conus lividus (V) [66,[72][73][74]. In particular, LvIA and LvIF are being intensively studied, have exhibited great binding ability to the α3β2 nAChR receptor and have great potential as new candidate tools for studying α3β2 nAChR-related neurophysiology and pharmacology [66,72].…”

Section: Structural and Functional Studies Of Conotoxins With Their R...mentioning

confidence: 99%

Biomedical Potential of the Neglected Molluscivorous and Vermivorous Conus Species

Zhao

Antunes

2022

Marine Drugs

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Within the Conidae family, the piscivorous Conus species have been a hotspot target for drug discovery. Here, we assess the relevance of Conus and their other feeding habits, and thus under distinctive evolutionary constraints, to highlight the potential of neglected molluscivorous and vermivorous species in biomedical research and pharmaceutical industry. By singling out the areas with inadequate Conus disquisition, such as the Tamil Nadu Coast and the Andaman Islands, research resources can be expanded and better protected through awareness. In this study, 728 Conus species and 190 species from three other genera (1 from Californiconus, 159 from Conasprella and 30 from Profundiconus) in the Conidae family are assessed. The phylogenetic relationships of the Conidae species are determined and their known feeding habits superimposed. The worm-hunting species appeared first, and later the mollusc- and fish-hunting species were derived independently in the Neogene period (around 23 million years ago). Interestingly, many Conus species in the warm and shallow waters become polyphagous, allowing them to hunt both fish and worms, given the opportunities. Such newly gained trait is multi originated. This is controversial, given the traditional idea that most Conus species are specialized to hunt certain prey categories. However, it shows the functional complexity and great potential of conopeptides from some worm-eating species. Pharmaceutical attempts and relevant omics data have been differentially obtained. Indeed, data from the fish-hunting species receive strong preference over the worm-hunting ones. Expectedly, conopeptides from the fish-hunting species are believed to include the most potential candidates for biomedical research. Our work revisits major findings throughout the Conus evolution and emphasizes the importance of increasing omics surveys complemented with further behavior observation studies. Hence, we claim that Conus species and their feeding habits are equally important, highlighting many places left for Conus exploration worldwide. We also discuss the Conotoxin drug discovery potentials and the urgency of protecting the bioresources of Conus species. In particular, some vermivorous species have demonstrated great potential in malaria therapy, while other conotoxins from several worm- and mollusc-eating species exhibited explicit correlation with SARS-CoV-2. Reclaiming idle data with new perspectives could also promote interdisciplinary studies in both virological and toxicological fields.

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Characterization of an α 4/7-Conotoxin LvIF from Conus lividus That Selectively Blocks α3β2 Nicotinic Acetylcholine Receptor

Cited by 7 publications

References 56 publications

Marine natural products

Marine natural products

Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications

Biomedical Potential of the Neglected Molluscivorous and Vermivorous Conus Species

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