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(Dap22)-ShK (ShK Dap22) peptide is a synthetic derivative of the well-known ShK toxin (Stichodactyla helianthus neurotoxin) isolated from the venom of the Carribean sea anemone Stoichactis helianthus. Wild-type ShK blocks voltage-gated Kv1.1, Kv1.3, Kv1.4 and Kv1.6 channels at equal subnanomolar concentrations. In (Dap22)-ShK, lysine22 has been replaced by a diaminopropionic acid (Dap) residue that greatly improves the selectivity of the peptide for the voltage-gated potassium channel Kv1.3 (IC50 around 23 pM)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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Peptides & proteins
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Limit of Detection:
4012.8 Da
Robbins JR., et al. (2005) Hypoxia modulates early events in T cell receptor-mediated activation in human T lymphocytes via Kv1.3 channels. J Physiol.; Norton RS., et al. (2004) Potassium channel blockade by the sea anemone toxin ShK for the treatment of multiple sclerosis and other autoimmune diseases. Curr Med Chem.; Middleton RE., et al. (2003) Substitution of a single residue in Stichodactyla helianthus peptide, ShK-Dap22, reveals a novel pharmacological profile. Biochemistry.; Lanigan MD., et al. (2002) Mutating a critical lysine in ShK toxin alters its binding configuration in the pore-vestibule region of the voltage-gated potassium channel, Kv1.3. Biochemistry.; Beeton C., et al. (2001) Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proc Natl Acad Sci USA.; Kalman K, et al. (1998) ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J Biol Chem.