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2000
Volume 21, Issue 8
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Background

Blocking Kv 1.2 and Kv 1.3 potassium channels using scorpion venom-derived toxins holds potential therapeutic value. These channels are implicated in autoimmune diseases such as neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes.

Objectives

The present work aims at the discovery and activity analysis of potassium channel blockers (KTxs) from the cDNA library derived from the venom gland of Iranian scorpion ().

Methods

The sequence regarding potassium channel blockers were extracted based on Gene Ontology for venom gland. Homology analyses, superfamily, family, and evolutionary signatures of KTxs (H.L KTxs) were determined by using BLASTP, COBALT, PROSITE, and InterPro servers. The predicted 3D structures of H.L KTxs were superimposed against their homologs to predict structure activity relationship. Molecular docking analysis was also performed to predict the binding affinity of H.L KTxs to Kv 1.2 and Kv 1.3 channels. Finally, the toxicity was predicted.

Results

Seven H.L KTxs, designated as Leptukalin, were extracted from the cDNA library of venom gland. Homology analyses proved that they can act as potassium channel blockers and they belong to the superfamily and family of Scorpion Toxin-like and Short-chain scorpion toxins, respectively. Structural alignment results confirmed the activity of H.L KTxs. Binding affinity of all H.L KTxs to Kv 1.2 and Kv 1.3 channels ranged from -4.4 to -5.5 and -4 to -5.7 Kcal/mol, respectively. toxicity assay showed that Leptukalin 3, Leptukalin 5, and Leptukalin 7 were non-toxic.

Conclusion

Three non-toxic KTxs, Leptukalin 3, 5, and 7, were successfully discovered from the cDNA library of venom gland. Gathering all data together, the discovered peptides are promising potassium channel blockers. Accordingly, Leptukalin 3, 5, and 7 could be suggested for complementary studies and mouse model of autoimmune diseases.

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In silico Discovery of Leptukalins, The New Potassium Channel Blockers from the Iranian Scorpion, Hemiscorpius Lepturus
Curr. Computeraided Drug Des. 21, 1080 (2025); https://doi.org/10.2174/0115734099309285240912113303
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  • Article Type:     Research Article
Keyword(s): autoimmune diseases; Hemiscorpius lepturus; In silico discovery; leptukalin; peptides; potassium channel blockers; scorpion; venom

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