Cvill6 and Cvill7: Potent and Selective Peptide Blockers of Kv1.2 Ion Channel Isolated from Mexican Scorpion <i>Centruroides villegasi</i>

Cvill6 and Cvill7: Potent and Selective Peptide Blockers of Kv1.2 Ion Channel Isolated from Mexican Scorpion <i>Centruroides villegasi</i>

Scorpion venoms are a rich source of peptides that modulate the activity of ion channels and can serve as a new drug for channelopathies. Cvill6 and Cvill7 are two new peptides isolated from the venom of <i>Centruroides villegasi</i> with MW of 4277 Da and 4287 Da and they consist of 38...

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Main Authors: Kashmala Shakeel, Muhammad Umair Naseem, Timoteo Olamendi-Portugal, Fernando Z. Zamudio, Lourival Domingos Possani, Gyorgy Panyi
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Toxins
Subjects:
α-KTx
<i>Centruroides villegasi</i> peptides
Kv1.2
Kv1.3
KCa3.1
patch-clampelectrophysiology
Online Access:https://www.mdpi.com/2072-6651/17/6/279
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Summary:Scorpion venoms are a rich source of peptides that modulate the activity of ion channels and can serve as a new drug for channelopathies. Cvill6 and Cvill7 are two new peptides isolated from the venom of <i>Centruroides villegasi</i> with MW of 4277 Da and 4287 Da and they consist of 38 and 39 amino acids, respectively, including six cysteines. Sequence alignment revealed high similarity with members of the α-KTx2 subfamily of potassium channel toxins. In electrophysiology, Cvill7 potently inhibited Kv1.2 ion channels with an IC<sub>50</sub> of 16 pM and Kv1.3 with an IC<sub>50</sub> of 7.2 nM. In addition, it exhibited partial activity on KCa3.1 and Kv1.1, with ~16% and ~34% inhibition at 100 nM, respectively. In contrast, Cvill6 blocked Kv1.2 with low affinity (IC<sub>50</sub> of 3.9 nM) and showed modest inhibition of Kv1.3 (~11%) and KCa3.1 (~27%) at 100 nM concentration. Neither peptide showed any activity against other K<sup>+</sup> channels tested in this study (Kv1.5, Kv11.1, KCa1.1, and KCa2.2). Notably, Cvill7 has a remarkable affinity for Kv1.2 and high selectivity of 450-fold over Kv1.3 and 12,000-fold over Kv1.1. These pharmacological properties make Cvill7 a potential candidate to target Kv1.2 gain of function (GOF)-related channelopathies such as epilepsy.
ISSN:2072-6651

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