A three-residue, continuous binding epitope peptidomimetic of ShK toxin as a Kv1.3 inhibitor

The ShK toxin is a polypeptide that blocks the Kv1.3 potassium channel in T-lymphocytes and has been identified as a potential therapeutic for multiple sclerosis. ShK is well characterised in terms of structure and binding, offering an attractive target for the design of structural and functional mimetics. Building on our previous success in developing rationally designed peptidomimetics of ShK, we report a novel mimetic of the K22–Y23–R24 residues of the peptide. The mimetic was shown to inhibit the Kv1.3 channel with moderate activity.