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First chemical synthesis of a scorpion alpha-toxin affecting sodium channels: the Aah i toxin of Androctonus australis hector


First chemical synthesis of a scorpion alpha-toxin affecting sodium channels: the Aah i toxin of Androctonus australis hector



Journal of Peptide Science: An Official Publication of the European Peptide Society 10(11): 666-677



ISSN/ISBN: 1075-2617

PMID: 15568681

DOI: 10.1002/psc.582

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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Accession: 049085967

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