Aah-II

AaH-II was originally discovered from the venom of the scorpion Androctonus australis Hector and belongs to alpha-toxins. It is a 64 amino-acid peptide that comprises four disulfide bonds and structured according a beta1-alpha-beta2-beta3 scaffold. Iodinated AaH-II binds with a 3 nM affinity to axolemma from rat Central Nervous System (DeVries and Lazdunski, 1982) . In frog myelinated nerve fibres, AaH-II prolongs the inactivation time constants of the inward Na+ current and induces a persistent current component (Benoit & Dubois, 1986) . By these two effects combined, AaH-II causes prolonged action potentials and thereby decreased firing frequencies. These effects are susceptible to produce paralysis, cardiac arrhythmia and death, including in humans (Bosmans & Tytgat, 2007) . Concerning the selectivity, the reported EC50 values for slowing channel inactivation are 3 nM for rat Nav1.2 and 2 nM for rat Nav1.4 channels (Alami et al., 2003) . The EC50 value on Nav1.7 is 52 nM. At the functional level, AaH-II was shown to bind onto the voltage-sensor of domain IV to block fast inactivation by trapping a deactivated state. (Clairfeuille et al., 2019) . Smartox now proposes the synthetic version of AaH-II.