Optimizing ShK: A Potassium Channel Blocking Peptide Derived from the Sea Anemone Stichodactyla helianthus, for Clinical Devel

Beeton C, Smith BJ, Sabo JK, Crossley G, Nugent D, Khaytin I, Chi V, Chandy KG, Pennington MW, Norton RS. The D-diastereomer of ShK toxin selectively blocks voltage-gated K+ channels and inhibits T lymphocyte proliferation. J Biol Chem. 2008 Jan 11;283(2):988-97.

Beeton C, Pennington MW, Wulff H, Singh S, Nugent D, Crossley G, Khaytin I, Calabresi PA, Chen CY, Gutman GA, Chandy KG. Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases. Mol Pharmacol. 2005 Apr;67(4):1369-81.

Norton RS, Pennington MW, Wulff H. Potassium channel blockade by the sea anemone toxin ShK for the treatment of multiple sclerosis and other autoimmune diseases. Curr Med Chem. 2004 Dec;11(23):3041-52.

Beeton C, Wulff H, Singh S, Botsko S, Crossley G, Gutman GA, Cahalan MD, Pennington M, Chandy KG. A novel fluorescent toxin to detect and investigate Kv1.3 channel up-regulation in chronically activated T lymphocytes.J Biol Chem. 2003 Mar 14;278(11):9928-37.

Lanigan MD, Kalman K, Lefievre Y, Pennington MW, Chandy KG, Norton RS. 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. 2002 Oct 8;41(40):11963-71.

Lanigan MD, Pennington MW, Lefievre Y, Rauer H, Norton RS. Designed peptide analogues of the potassium channel blocker ShK toxin. Biochemistry. 2001 Dec 25;40(51):15528-37.

Beeton C, Wulff H, Barbaria J, Clot-Faybesse O, Pennington M, Bernard D, Cahalan MD, Chandy KG, Béraud E. Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13942-7.

Lanigan MD, Tudor JE, Pennington MW, Norton RS. A helical capping motif in ShK toxin and its role in helix stabilization. Biopolymers. 2001 Apr 5;58(4):422-36.

Pennington MW, Lanigan MD, Kalman K, Mahnir VM, Rauer H, McVaugh CT, Behm D, Donaldson D, Chandy KG, Kem WR, Norton RS. Role of disulfide bonds in the structure and potassium channel blocking activity of ShK toxin. Biochemistry. 1999 Nov 2;38(44):14549-58.

Rauer H, Pennington M, Cahalan M, Chandy KG. Structural conservation of the pores of calcium-activated and voltage-gated potassium channels determined by a sea anemone toxin. J Biol Chem. 1999 Jul 30;274(31):21885-92.

Kalman K, Pennington MW, Lanigan MD, Nguyen A, Rauer H, Mahnir V, Paschetto K, Kem WR, Grissmer S, Gutman GA, Christian EP, Cahalan MD, Norton RS, Chandy KG. ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J Biol Chem. 1998 Dec 4;273(49):32697-707.

Tudor JE, Pennington MW, Norton RS. Ionisation behaviour and solution properties of the potassium-channel blocker ShK toxin. Eur J Biochem. 1998 Jan 15;251(1-2):133-41.

Pennington MW, Mahnir VM, Khaytin I, Zaydenberg I, Byrnes ME, Kem WR. An essential binding surface for ShK toxin interaction with rat brain potassium channels. Biochemistry. 1996 Dec 24;35(51):16407-11.

Tudor JE, Pallaghy PK, Pennington MW, Norton RS. Solution structure of ShK toxin, a novel potassium channel inhibitor from a sea anemone. Nat Struct Biol. 1996 Apr;3(4):317-20.

Pennington MW, Mahnir VM, Krafte DS, Zaydenberg I, Byrnes ME, Khaytin I, Crowley K, Kem WR. :

Identification of three separate binding sites on SHK toxin, a potent inhibitor of voltage-dependent potassium channels in human T-lymphocytes and rat brain. Biochem Biophys Res Commun. 1996 Feb 27;219(3):696-701.

Pennington MW, Byrnes ME, Zaydenberg I, Khaytin I, de Chastonay J, Krafte DS, Hill R, Mahnir VM, Volberg WA, Gorczyca W, et al. Chemical synthesis and characterization of ShK toxin: a potent potassium channel inhibitor from a sea anemone. Int J Pept Protein Res. 1995 Nov;46(5):354-8.