ArticleThe Journal of biological chemistry2009
Rational design of alpha-conotoxin analogues targeting alpha7 nicotinic acetylcholine receptors: improved antagonistic activity by incorporation of proline derivatives.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 51 citations in OpenAlex.
- Nickel-Photocatalytic Deoxygenative Arylation toward β-Methyl-Branched α-Amino Acids.Organic letters · 2026Article
- Modular Synthesis of Dehydroprolines by an Energy-Transfer Enabled Cloke-Wilson Rearrangement.Angewandte Chemie (International ed. in English) · 2025Article
- In Silico Conotoxin Studies: Progress and Prospects.Molecules (Basel, Switzerland) · 2024Review
- Single Amino Acid Substitution in Loop1 Switches the Selectivity of α-Conotoxin RegIIA towards the α7 Nicotinic Acetylcholine Receptor.Marine drugs · 2024Article
- Fluorescent α-Conotoxin [Q1G, ΔR14]LvIB Identifies the Distribution ofMarine drugs · 2024Article
- Substitution of D-Arginine at Position 11 of α-RgIA Potently Inhibits α7 Nicotinic Acetylcholine Receptor.Marine drugs · 2023Article
- Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages.Marine drugs · 2022Article
- α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia.Toxins · 2020Review
- Identification of Crucial Residues in α-Conotoxin EI Inhibiting Muscle Nicotinic Acetylcholine Receptor.Toxins · 2019Article
- Article
- Effects of C-Terminal Carboxylation on α-Conotoxin LsIA Interactions with Human α7 Nicotinic Acetylcholine Receptor: Molecular Simulation Studies.Marine drugs · 2019Article
- Mutagenesis of α-Conotoxins for Enhancing Activity and Selectivity for Nicotinic Acetylcholine Receptors.Toxins · 2019Review
- Semisynthetic analogues of toxiferine I and their pharmacological properties at α7 nAChRs, muscle-type nAChRs, and the allosteric binding site of muscarinic M2 receptors.Journal of natural products · 2014Article
- Discovery, synthesis, and structure-activity relationships of conotoxins.Chemical reviews · 2014Review
- Conotoxins targeting nicotinic acetylcholine receptors: an overview.Marine drugs · 2014Review
- Discovery of a potent and selective α3β4 nicotinic acetylcholine receptor antagonist from an α-conotoxin synthetic combinatorial library.Journal of medicinal chemistry · 2014Article
- Structure-function elucidation of a new α-conotoxin, Lo1a, from Conus longurionis.The Journal of biological chemistry · 2014Article
- Nicotine aversion: Neurobiological mechanisms and relevance to tobacco dependence vulnerability.Neuropharmacology · 2014Review
- Blockade of neuronal α7-nAChR by α-conotoxin ImI explained by computational scanning and energy calculations.PLoS computational biology · 2011Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that belong to the superfamily of Cys loop receptors. Valuable insight into the orthosteric ligand binding to nAChRs in recent years has been obtained from the crystal structures of acetylcholine-binding proteins (AChBPs) that share significant sequence homology with the amino-terminal domains of the nAChRs. alpha-Conotoxins, which are isolated from the venom of carnivorous marine snails, selectively inhibit the signaling of neuronal nAChR subtypes. Co-crystal structures of alpha-conotoxins in complex with AChBP show that the side chain of a highly conserved proline residue in these toxins is oriented toward the hydrophobic binding pocket in the AChBP but does not have direct interactions with this pocket. In this study, we have designed and synthesized analogues of alpha-conotoxins ImI and PnIA[A10L], by introducing a range of substituents on the Pro(6) residue in these toxins to probe the importance of this residue for their binding to the nAChRs. Pharmacological characterization of the toxin analogues at the alpha(7) nAChR shows that although polar and charged groups on Pro(6) result in analogues with significantly reduced antagonistic activities, analogues with aromatic and hydrophobic substituents in the Pro(6) position exhibit moderate activity at the receptor. Interestingly, introduction of a 5-(R)-phenyl substituent at Pro(6) in alpha-conotoxin ImI gives rise to a conotoxin analogue with a significantly higher binding affinity and antagonistic activity at the alpha(7) nAChR than those exhibited by the native conotoxin.
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Registered trials
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.