The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6.
J Med Chem
; 61(4): 1730-1736, 2018 02 22.
Article
em En
| MEDLINE
| ID: mdl-29378414
ABSTRACT
We report the chemical synthesis of scorpion toxin Cn2, a potent and highly selective activator of the human voltage-gated sodium channel NaV1.6. In an attempt to decouple channel activation from channel binding, we also synthesized the first analogue of this toxin, Cn2[E15R]. This mutation caused uncoupling of the toxin's excitatory and depressant activities, effectively resulting in a NaV1.6 inhibitor. In agreement with the in vitro observations, Cn2[E15R] is antinociceptive in mouse models of NaV1.6-mediated pain.
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Base de dados:
MEDLINE
Assunto principal:
Venenos de Escorpião
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Toxinas Biológicas
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Mutação Puntual
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Canal de Sódio Disparado por Voltagem NAV1.6
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Analgésicos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article