< Back to previous page

Publication

Expanding the pharmacological profile of κ-hefutoxin 1 and analogues: A focus on the inhibitory effect on the oncogenic channel Kv10.1

Journal Contribution - Journal Article

Peptide toxins, such as scorpion peptides, are interesting lead compounds in the search for novel drugs. In this paper, the focus is on the scorpion peptide κ-hefutoxin 1. This peptide displays a cysteine-stabilized helix-loop-helix fold (CSα/α) and is known to be a weak Kv1.x inhibitor. Due to the low affinity of κ-hefutoxin 1 for these channels, it is assumed that the main target(s) of κ-hefutoxin 1 remain(s) unknown. In order to identify novel targets, electrophysiological measurements and antifungal assays were performed. The effect of κ-hefutoxin 1 was previously evaluated on a panel of 11 different voltage-gated potassium channels. Here, we extended this target screening with the oncogenic potassium channel Kv10.1. κ-Hefutoxin 1 was able to inhibit this channel in a dose-dependent manner (IC50∼26μM). Although the affinity is rather low, this is the first peptide toxin ever described to be a Kv10.1 inhibitor. The structure-activity relationship of κ-hefutoxin 1 on Kv10.1 was investigated by testing eight κ-hefutoxin 1 variants using the two-electrode voltage clamp technique. Several important amino acid residues were identified; the functional dyad residues (Tyr5 and Lys19), N-terminal residues (Gly1 and His2) and the amidated C-terminal residue (Cys22). Since the CSα/α fold is also found in a class of antifungal plant peptides, the α-hairpinines, we investigated the antifungal activity of κ-hefutoxin 1. κ-Hefutoxin 1 showed low activity against the plant pathogen Fusarium culmorum and no activity against three other yeast and fungal species, even at high concentrations (∼100μM).
Journal: Peptides
ISSN: 0196-9781
Volume: 98
Pages: 43 - 50
Publication year:2017
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:1
CSS-citation score:1
Authors:International
Authors from:Government, Higher Education