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 language | English |
|---|---|
| Pages (from-to) | 666-677 |
| Number of pages | 12 |
| Journal | Journal of Peptide Science |
| Volume | 10 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2004 |
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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
Cite this
First chemical synthesis of a scorpion α-toxin affecting sodium channels : The Aah I toxin of Androctonus australis hector. / M'Barek, Sarrah; Fajloun, Ziad; Cestèle, Sandrine; Devaux, Christiane; Mansuelle, Pascal; Mosbah, Amor; Jouirou, Besma; Mantegazza, Massimo; Van Rietschoten, Jurphaas; El Ayeb, Mohamed; Rochat, Hervé; Sabatier, Jean Marc; Sampieri, Francois.
In: Journal of Peptide Science, Vol. 10, No. 11, 11.2004, p. 666-677.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=8644278057&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8644278057&partnerID=8YFLogxK
U2 - 10.1002/psc.582
DO - 10.1002/psc.582
M3 - Article
VL - 10
SP - 666
EP - 677
JO - Journal of Peptide Science
JF - Journal of Peptide Science
SN - 1075-2617
IS - 11
ER -