First chemical synthesis of a scorpion α-toxin affecting sodium channels: The Aah I toxin of Androctonus australis hector

Sarrah M'Barek, Ziad Fajloun, Sandrine Cestèle, Christiane Devaux, Pascal Mansuelle, Amor Mosbah, Besma Jouirou, Massimo Mantegazza, Jurphaas Van Rietschoten, Mohamed El Ayeb, Hervé Rochat, Jean Marc Sabatier, Francois Sampieri

Research output: Contribution to journalArticlepeer-review

Abstract

Aah I is a 63-residue α-toxin isolated from the venom of the Buthidae scorpion Androctonus australis hector, which is considered to be the most dangerous species. We report here the first chemical synthesis of Aah I by the solid-phase method, using a Fmoc strategy. The synthetic toxin I (sAah I) was renatured in DMSO-Tris buffer, purified and subjected to thorough analysis and comparison with the natural toxin. The sAah I showed physico-chemical (CD spectrum, molecular mass, HPLC elution), biochemical (amino-acid composition, sequence), immunochemical and pharmacological properties similar to those of the natural toxin. The synthetic toxin was recognized by a conformation-dependent monoclonal anti-Aah I antibody, with an IC50 value close to that for the natural toxin. Following intracerebroventricular injection, the synthetic and the natural toxins were similarly lethal to mice. In voltage-clamp experiments, Nav 1.2 sodium channel inactivation was inhibited by the application of sAah I or of the natural toxin in a similar way. This work describes a simple protocol for the chemical synthesis of a scorpion α-toxin, making it possible to produce structural analogues in time.

Original languageEnglish
Pages (from-to)666-677
Number of pages12
JournalJournal of Peptide Science
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 2004

Keywords

  • Aah I
  • Oxidation/refolding
  • Scorpion α-toxin
  • Sodium channel
  • Solid-phase peptide synthesis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

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