(Dap22)-ShK – Ion Channels and Transporters

(Dap22)-ShK (ShK Dap22) peptide is a synthetic derivative of the well-known ShK toxin #08SHK001 (Stichodactyla helianthus neurotoxin) isolated from the venom of the Carribean sea anemone Stoichactis helianthus. Wild-type ShK blocks potently Kv1.3 (KCNA3), Kv1.1 (KCNA1), Kv1.4 (KCNA4), and Kv1.6 (KCNA6) respectively with a Kd of 11 pM,16 pM, 312 pM and 165 pM. In (Dap22)-ShK, lysine22 has been replaced by a diaminopropionic acid (Dap) residue that greatly improves the selectivity of the peptide for the voltage-gated potassium channel Kv1.3 (IC50 around 23 pM) against Kv1.1 (1.8 nM), Kv1.4 (37 nM) and Kv1.6 (10 nM) channels. The high selectivity of (Dap22)-Shk is achieved thanks to the strong binding between the Dap and His404 / Asp386 residues of Kv1.3 channel. (Dap22)-ShK inhibits T cell proliferation induced by anti-CD3 at subnanomolar concentrations.

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