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Du venin de cônes au médicament.  Auteur(s): Dutertre S., Benoit Evelyne, Molgo Jordi (Autres publications) , 2014 Ref HAL: hal-01089751_v1 Résumé: Les venins de cônes sont très prometteurs comme source de nouveaux médicaments. Mais démêler leur pharmacologie complexe et isoler leurs composants actifs, parfois mineurs, parmi les centaines de molécules présentes dans un seul venin sont des tâches difficiles. Avec l’intégration des nouvelles technologies de séquençage de l’ADN, de protéomique et de criblage à haut débit, la découverte de molécules d’intérêt thérapeutique s'accélère. |
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Intraspecific variations in Conus geographus defence-evoked venom and estimation of the human lethal dose. Auteur(s): Dutertre S., Ai-Hua Jin, Alewood Paul F., Lewis Richard J. (Article) Publié: Toxicon, vol. 91 p.135-144 (2014) Ref HAL: hal-01089713_v1 DOI: 10.1016/j.toxicon.2014.09.011 Résumé: Conus geographus is the most dangerous cone snail species known, with reported human fatality rates as high as 65%. Crude venom gland extracts have been used to determine animal LD50 and to aid the isolation of several potent paralytic toxins. However, not only is the composition of injected venoms known to differ significantly from that in dissected venom glands, but also to vary according to predatory or defensive stimuli. Therefore, to study the venom that is directly relevant to human envenomation, the defense-evoked venom of several specimens of C. geographus was collected and analyzed by standard LC–MS methods. The molecular composition of individual defense-evoked venom showed significant intraspecific variations, but a core of paralytic conotoxins including α-GI, α-GII, μ-GIIIA, ω-GVIA and ω-GVIIA was always present in large amounts, consistent with the symptomology and high fatality rate in humans. Differences between injected and dissected venoms obtained from the same specimen were also evident. Interestingly, an apparent linear correlation between the dry weight/volume of injected venom and the size of the shell allowed extrapolation to a human lethal dose (0.038–0.029 mg/kg) from an historic fatal case of C. geographus envenomation, which may help in the management of future victims. |
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Cone snail venomics: from novel biology to novel therapeutics. Auteur(s): Prashanth Jutty Rajan, Brust Andreas, Ai-Hua Jin, Alewood Paul F, Dutertre S., Lewis Richard J (Article) Publié: Future Medicinal Chemistry, vol. 6 p.1659-1675 (2014) Ref HAL: hal-01089383_v1 DOI: 10.4155/FMC.14.99 Résumé: Peptide neurotoxins from cone snails called conotoxins are renowned for their therapeutic potential to treat pain and several neurodegenerative diseases . Inefficient assay-guided discovery methods have been replaced by high-throughput bioassaysintegrated with advanced MS and next-generation sequencing, ushering in the era of ‘venomics’. In this review, we focus on the impact of venomics on the understanding of cone snail biology as well as the application of venomics to accelerate the discovery of new conotoxins. We also discuss the continued importance of medicinal chemistry approaches to optimize conotoxins for clinical use, with a descriptive case study of MrIA featured. |
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Venomics in medicinal chemistry. Auteur(s): Dutertre S. (Article) Publié: Future Medicinal Chemistry, vol. 6 p.1609-1610 (2014) Ref HAL: hal-01089730_v1 DOI: 10.4155/FMC.14.117 Résumé: Venom peptides mainly target ion channels, but also GPCRs, transporters and enzymes with high affinity and exquisite selectivity. The intermediate size of these peptidic toxins and their proteinaceous nature make them particularly suited formedicinal chemistry. |
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Du venin au médicament Auteur(s): Dutertre S. (Autres publications) , 2014 Ref HAL: hal-01089352_v1 Résumé: Serpents, scorpions, araignées, cônes…Ces animaux sécrètent des venins extrêmement puissants, leur permettant de tuer leurs proies en quelques secondes. Mais ces élixirs mortels sont aussi une formidable source d’espoirs : les chercheurs étudient ces venins pour mettre au point de nouveaux médicaments. |