From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei

Tânia C. Gonçalves 1, 2 Evelyne Benoit 2, 3 Michael Kurz Laetitia Lucarain Sophie Fouconnier Stéphanie Combemale 4 Lucie Jaquillard 4 Brigitte Schombert Jean‐marie Chambard Rachid Boukaiba 5 Gerhard Hessler 6 Andrees Bohme Laurent Bialy Stéphane Hourcade Rémy Beroud 4 Michel de Waard 7 Denis Servent 2 Michel Partiseti 1
1 Sanofi R & D, Integrated Drug Discovery, In Vitro Biology & Pharmacology
2 SIMoS - Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO)
3 Neuro-PSI - Institut des Neurosciences de Paris-Saclay
4 Smartox Biotechnology
5 Sanofi R & D, Integrated Drug Discovery, In Vitro Biology & Pharmacology
6 Sanofi-Aventis Deutschland GmbH
7 INSERM U836, équipe 3, Canaux calciques, fonctions et pathologies
GIN - Grenoble Institut des Neurosciences
Abstract : The NaV 1.7 channel is highly expressed in dorsal root ganglia of the sensory nervous system and plays a central role in the pain signalling process. We investigated a library prepared from original venoms of 117 different animals to identify new selective inhibitors of this target. EXPERIMENTAL APPROACH : We used high throughput screening of a large venom collection using automated patch-clamp experiments on human voltage-gated sodium channel subtypes and then in vitro and in vivo electrophysiological experiments to characterize the active peptides that have been purified, sequenced, and chemically synthesized. Analgesic effects were evaluated in vivo in mice models. The pharmacological profile of CyrTx-1a paves the way for further molecular engineering aimed to optimize the potential antinociceptive properties of this peptide.
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Journal articles
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https://hal-cea.archives-ouvertes.fr/cea-02121632
Contributor : Evelyne Benoit <>
Submitted on : Monday, May 6, 2019 - 4:40:23 PM
Last modification on : Wednesday, January 8, 2020 - 1:37:26 AM

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Tânia C. Gonçalves, Evelyne Benoit, Michael Kurz, Laetitia Lucarain, Sophie Fouconnier, et al.. From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei. British Journal of Pharmacology, Wiley, 2019, 176 (9), pp.1298-1314. ⟨10.1111/bph.14628⟩. ⟨cea-02121632⟩

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