TY - JOUR
T1 - First chemical synthesis of a scorpion α-toxin affecting sodium channels
T2 - The Aah I toxin of Androctonus australis hector
AU - M'Barek, Sarrah
AU - Fajloun, Ziad
AU - Cestèle, Sandrine
AU - Devaux, Christiane
AU - Mansuelle, Pascal
AU - Mosbah, Amor
AU - Jouirou, Besma
AU - Mantegazza, Massimo
AU - Van Rietschoten, Jurphaas
AU - El Ayeb, Mohamed
AU - Rochat, Hervé
AU - Sabatier, Jean Marc
AU - Sampieri, Francois
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
KW - Aah I
KW - Oxidation/refolding
KW - Scorpion α-toxin
KW - Sodium channel
KW - Solid-phase peptide synthesis
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U2 - 10.1002/psc.582
DO - 10.1002/psc.582
M3 - Article
C2 - 15568681
AN - SCOPUS:8644278057
VL - 10
SP - 666
EP - 677
JO - Journal of Peptide Science
JF - Journal of Peptide Science
SN - 1075-2617
IS - 11
ER -