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.
Harvey
Andrew J
AJ
The Walter and Eliza Hall, Institute of Medical Research, Biotechnology Centre, 4 Research Avenue, La Trobe R and D Park, Bundoora 3086, Australia.
Gable
Robert W
RW
Baell
Jonathan B
JB
D000818:Animals; D002460:Cell Line; D003064:Cnidarian Venoms / Q000737:chemistry*; D000939:Epitopes; D051664:Kv1.3 Potassium Channel; D051379:Mice; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000235:genetics; D014162:Transfection
D003064:Cnidarian Venoms; D000939:Epitopes; C496974:Kcna3 protein, mouse; D051664:Kv1.3 Potassium Channel; D009842:Oligopeptides; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C095391:ShK neurotoxin