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Title

Identification, structural and pharmacological characterization of τ-CnVA, a conopeptide that selectively interacts with somatostatin sst3 receptor

Authors
Petrel, C
Hocking, H G
Reynaud, M
Upert, G
Favreau, Ph
Biass, D
Peigneur, S
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Published in Biochemical Pharmacology. 2013, vol. 85, no. 11, p. 1663-71
Abstract Conopeptides are a diverse array of small linear and reticulated peptides that interact with high potency and selectivity with a large diversity of receptors and ion channels. They are used by cone snails for prey capture or defense. Recent advances in venom gland transcriptomic and venom peptidomic/proteomic technologies combined with bioactivity screening approaches lead to the identification of new toxins with original pharmacological profiles. Here, from transcriptomic/proteomic analyses of the Conus consors cone snail, we identified a new conopeptide called τ-CnVA, which displays the typical cysteine framework V of the T1-conotoxin superfamily. This peptide was chemically synthesized and its three-dimensional structure was solved by NMR analysis and compared to that of TxVA belonging to the same family, revealing very few common structural features apart a common orientation of the intercysteine loop. Because of the lack of a clear biological function associated with the T-conotoxin family, τ-CnVA was screened against more than fifty different ion channels and receptors, highlighting its capacity to interact selectively with the somatostatine sst3 receptor. Pharmacological and functional studies show that τ-CnVA displays a micromolar (Ki of 1.5μM) antagonist property for the sst3 receptor, being currently the only known toxin to interact with this GPCR subfamily.
Keywords Amino Acid SequenceAnimalsCHO CellsCalcium/metabolismConotoxins/chemistry/pharmacologyCricetinaeCricetulusIon Channels/metabolismModels, MolecularMolecular Sequence DataNuclear Magnetic Resonance, BiomolecularProtein ConformationProteomicsReceptors, Somatostatin/drug effectsTranscriptomeXenopus laevis
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PMID: 23567999
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Research group Hiv (835)
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PETREL, C et al. Identification, structural and pharmacological characterization of τ-CnVA, a conopeptide that selectively interacts with somatostatin sst3 receptor. In: Biochemical Pharmacology, 2013, vol. 85, n° 11, p. 1663-71. https://archive-ouverte.unige.ch/unige:43128

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Deposited on : 2014-12-11

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