Spiroindolines Identify the Vesicular Acetylcholine Transporter as a Novel Target for Insecticide Action
| العنوان: | Spiroindolines Identify the Vesicular Acetylcholine Transporter as a Novel Target for Insecticide Action |
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| المؤلفون: | Molleyres Louis-Pierre, Sheetal Shah, Elizabeth A. Hirst, Roberts Richard Spurring, Anthony J. Flemming, Penny Cutler, Paul A. Worthington, Carole Patricia Syngenta Ltd. Stanger, David John Hughes, Elke Maria Hillesheim, Thomas Pitterna, John David Windass, Fredrik Cederbaum, Ralph Clover, Thomas Flury, Min Shi, Andrew J. Crossthwaite, Ann E. Sluder, Mike Robinson, Richard A. Currie, Fergus Gerard Paul Earley, Peter Maienfisch, Jérôme Yves Cassayre |
| المصدر: | PLoS ONE PLoS ONE, Vol 7, Iss 5, p e34712 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Insecticides, Genetic Screens, Insecta, Vesamicol, Vesicular Acetylcholine Transport Proteins, ved/biology.organism_classification_rank.species, lcsh:Medicine, Plasma protein binding, PC12 Cells, Biochemistry, chemistry.chemical_compound, Protein Isoforms, lcsh:Science, Cells, Cultured, Radiochemistry, Multidisciplinary, Molecular Structure, Antinematodal Agents, Genetically Modified Organisms, Drosophila Melanogaster, Agriculture, Neurochemistry, Animal Models, Chemistry, Radioactivity, Caenorhabditis Elegans, Larva, Neurochemicals, Agrochemicals, Genetic Engineering, Synthetic Chemistry, Acetylcholine, Protein Binding, Research Article, Biotechnology, medicine.drug, Protein family, Molecular Sequence Data, Biology, Heterocyclic Compounds, 4 or More Rings, Model Organisms, Genetic Mutation, Vesicular acetylcholine transporter, Genetics, medicine, Animals, Spiro Compounds, Amino Acid Sequence, Pesticides, Caenorhabditis elegans Proteins, Model organism, Sequence Homology, Amino Acid, ved/biology, lcsh:R, Organic Chemistry, Organic Synthesis, Biological Transport, Rats, chemistry, Small Molecules, Mutagenesis, lcsh:Q, Pest Control, Molecular Neuroscience, Animal Genetics, Function (biology), Neuroscience |
| الوصف: | The efficacy of all major insecticide classes continues to be eroded by the development of resistance mediated, in part, by selection of alleles encoding insecticide insensitive target proteins. The discovery of new insecticide classes acting at novel protein binding sites is therefore important for the continued protection of the food supply from insect predators, and of human and animal health from insect borne disease. Here we describe a novel class of insecticides (Spiroindolines) encompassing molecules that combine excellent activity against major agricultural pest species with low mammalian toxicity. We confidently assign the vesicular acetylcholine transporter as the molecular target of Spiroindolines through the combination of molecular genetics in model organisms with a pharmacological approach in insect tissues. The vesicular acetylcholine transporter can now be added to the list of validated insecticide targets in the acetylcholine signalling pathway and we anticipate that this will lead to the discovery of novel molecules useful in sustaining agriculture. In addition to their potential as insecticides and nematocides, Spiroindolines represent the only other class of chemical ligands for the vesicular acetylcholine transporter since those based on the discovery of vesamicol over 40 years ago, and as such, have potential to provide more selective tools for PET imaging in the diagnosis of neurodegenerative disease. They also provide novel biochemical tools for studies of the function of this protein family. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2c2a0b11ab80f39abc619ae2a57debbTest https://doi.org/10.1371/journal.pone.0034712Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a2c2a0b11ab80f39abc619ae2a57debb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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