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ID: ALA4715816

Journal: J Med Chem

Title: The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human Na1.6.

Authors: Israel MR,Thongyoo P,Deuis JR,Craik DJ,Vetter I,Durek T

Abstract: We report the chemical synthesis of scorpion toxin Cn2, a potent and highly selective activator of the human voltage-gated sodium channel Na1.6. 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 Na1.6 inhibitor. In agreement with the in vitro observations, Cn2[E15R] is antinociceptive in mouse models of Na1.6-mediated pain.

CiteXplore: 29378414

DOI: 10.1021/acs.jmedchem.7b01609