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

Abstract : Aah I is a 63-residue alpha-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, Na(v) 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 alpha-toxin, making it possible to produce structural analogues in time.
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Submitted on : Thursday, February 28, 2019 - 12:20:57 PM
Last modification on : Saturday, August 10, 2019 - 1:19:19 AM

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Sarrah M'Barek, Ziad Fajloun, Sandrine Cestèle, Christiane Devaux, Pascal Mansuelle, et al.. First chemical synthesis of a scorpion α-toxin affecting sodium channels: The Aah I toxin of Androctonus australis hector. Journal of Peptide Science, Wiley, 2004, 10 (11), pp.666-677. ⟨10.1002/psc.582⟩. ⟨pasteur-02052144⟩

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