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

Andrew J Harvey; Robert W Gable; Jonathan B Baell

doi:10.1016/j.bmcl.2005.05.014

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

Bioorg Med Chem Lett. 2005 Jul 1;15(13):3193-6. doi: 10.1016/j.bmcl.2005.05.014.

Authors

Andrew J Harvey¹, Robert W Gable, Jonathan B Baell

Affiliation

¹ The Walter and Eliza Hall, Institute of Medical Research, Biotechnology Centre, 4 Research Avenue, La Trobe R and D Park, Bundoora 3086, Australia.

PMID: 15935664
DOI: 10.1016/j.bmcl.2005.05.014

Abstract

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.

MeSH terms

Animals
Cell Line
Cnidarian Venoms / chemistry*
Epitopes
Kv1.3 Potassium Channel
Mice
Molecular Mimicry
Oligopeptides / chemistry
Oligopeptides / pharmacology*
Peptide Fragments / chemistry
Peptide Fragments / pharmacology
Potassium Channel Blockers / chemistry
Potassium Channel Blockers / pharmacology*
Potassium Channels, Voltage-Gated / antagonists & inhibitors*
Potassium Channels, Voltage-Gated / genetics
Transfection

Substances

Cnidarian Venoms
Epitopes
Kcna3 protein, mouse
Kv1.3 Potassium Channel
Oligopeptides
Peptide Fragments
Potassium Channel Blockers
Potassium Channels, Voltage-Gated
ShK neurotoxin