ArticleProceedings of the National Academy of Sciences of the United States of America2015
Cloning, synthesis, and characterization of αO-conotoxin GeXIVA, a potent α9α10 nicotinic acetylcholine receptor antagonist.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 107 citations in OpenAlex.
- αO-Conotoxin GeXIVA[1,2] Attenuates Paclitaxel-Induced Neurotoxicity by Suppressing Ferroptosis via the Nrf2/SLC7A11/GSH/GPX4 Pathway.Marine drugs · 2026Article
- Deep learning-driven discovery and mechanism of action study of a minimalist conopeptide targetingActa pharmaceutica Sinica. B · 2026Article
- Article
- Nicotinic acetylcholine receptors in pain modulation.Frontiers in pharmacology · 2026Review
- The role of acetylcholine and its receptors in tumor immune regulation: mechanisms and potential therapeutic targets.Molecular cancer · 2025Review
- Prediction of Specificity of α-Conotoxins to Subtypes of Human Nicotinic Acetylcholine Receptors with Semi-supervised Machine Learning.ACS chemical neuroscience · 2025Article
- α9 Nicotinic Acetylcholine Receptor Promotes Tumor Proliferation and Suppresses Ferroptosis in Triple-Negative Breast Cancer.Biomolecules · 2025Article
- Marine-derived bioactive compounds for neuropathic pain: pharmacology and therapeutic potential.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Diverse toxins exhibit a common binding mode to the nicotinic acetylcholine receptors.Biophysical journal · 2025Article
- Sustained Release of αO-Conotoxin GeXIVA[1,2] via Hydrogel Microneedle Patch for Chronic Neuropathic Pain Management.Marine drugs · 2025Article
- α9-Containing Nicotinic Acetylcholine Receptors Are Required for RgIA-5474 Attenuation of Chemotherapy-Induced Neuropathic Pain.ACS pharmacology & translational science · 2024Article
- Stapling Cysteine[2,4] Disulfide Bond of α-Conotoxin LsIA and Its Potential in Target Delivery.Marine drugs · 2024Article
- Chemical Synthesis and Insecticidal Activity Research Based on α-Conotoxins.Molecules (Basel, Switzerland) · 2024Article
- Article
- αO-Conotoxin GeXIVA[1,2] Reduced Neuropathic Pain and Changed Gene Expression in Chronic Oxaliplatin-Induced Neuropathy Mice Model.Marine drugs · 2024Article
- Exploring Cholinergic Compounds for Peripheral Neuropathic Pain Management: A Comprehensive Scoping Review of Rodent Model Studies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Nicotinic acetylcholine receptors: Therapeutic targets for novel ligands to treat pain and inflammation.Pharmacological research · 2023Review
- α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain.International journal of molecular sciences · 2023Review
- Inferring Pathways of Oxidative Folding from Prefolding Free Energy Landscapes of Disulfide-Rich Toxins.The journal of physical chemistry. B · 2023Article
- Peptides from the Sea AnemoneToxins · 2022Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
We identified a previously unidentified conotoxin gene from Conus generalis whose precursor signal sequence has high similarity to the O1-gene conotoxin superfamily. The predicted mature peptide, αO-conotoxin GeXIVA (GeXIVA), has four Cys residues, and its three disulfide isomers were synthesized. Previously pharmacologically characterized O1-superfamily peptides, exemplified by the US Food and Drug Administration-approved pain medication, ziconotide, contain six Cys residues and are calcium, sodium, or potassium channel antagonists. However, GeXIVA did not inhibit calcium channels but antagonized nicotinic AChRs (nAChRs), most potently on the α9α10 nAChR subtype (IC50 = 4.6 nM). Toxin blockade was voltage-dependent, and kinetic analysis of toxin dissociation indicated that the binding site of GeXIVA does not overlap with the binding site of the competitive antagonist α-conotoxin RgIA. Surprisingly, the most active disulfide isomer of GeXIVA is the bead isomer, comprising, according to NMR analysis, two well-resolved but uncoupled disulfide-restrained loops. The ribbon isomer is almost as potent but has a more rigid structure built around a short 310-helix. In contrast to most α-conotoxins, the globular isomer is the least potent and has a flexible, multiconformational nature. GeXIVA reduced mechanical hyperalgesia in the rat chronic constriction injury model of neuropathic pain but had no effect on motor performance, warranting its further investigation as a possible therapeutic agent.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.