{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:48:09Z","timestamp":1792180089256,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian National Research, Development, and Innovation Office","award":["K143071"],"award-info":[{"award-number":["K143071"]}]},{"name":"Hungarian National Research, Development, and Innovation Office","award":["K127931"],"award-info":[{"award-number":["K127931"]}]},{"name":"Tempus Public Foundation","award":["K143071"],"award-info":[{"award-number":["K143071"]}]},{"name":"Tempus Public Foundation","award":["K127931"],"award-info":[{"award-number":["K127931"]}]},{"name":"Richter Gedeon Talentum Foundation","award":["K143071"],"award-info":[{"award-number":["K143071"]}]},{"name":"Richter Gedeon Talentum Foundation","award":["K127931"],"award-info":[{"award-number":["K127931"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>The Kv1.3 channel has become a therapeutic target for the treatment of various diseases. Several Kv1.3 channel blockers have been characterized from scorpion venom; however, extensive studies require amounts of toxin that cannot be readily obtained directly from venoms. The Pichia\u00a0pastoris expression system provides a cost-effective approach to overcoming the limitations of chemical synthesis and E. coli recombinant expression. In this work, we developed an efficient system for the production of three potent Kv1.3 channel blockers from different scorpion venoms: Vm24, AnTx, and Ts6. Using the Pichia system, these toxins could be obtained in sufficient quantities (Vm24 1.6 mg\/L, AnTx 46 mg\/L, and Ts6 7.5 mg\/L) to characterize their biological activity. A comparison was made between the activity of tagged and untagged recombinant peptides. Tagged Vm24 and untagged AnTx are nearly equivalent to native toxins in blocking Kv1.3 (Kd = 4.4 pM and Kd = 0.72 nM, respectively), whereas untagged Ts6 exhibits a 53-fold increase in Kd (Kd = 29.1 nM) as compared to the native peptide. The approach described here provides a method that can be optimized for toxin production to develop more selective and effective Kv1.3 blockers with therapeutic potential.<\/jats:p>","DOI":"10.3390\/jof8111215","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:05:21Z","timestamp":1668654321000},"page":"1215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Recombinant Expression in Pichia pastoris System of Three Potent Kv1.3 Channel Blockers: Vm24, Anuroctoxin, and Ts6"],"prefix":"10.3390","volume":"8","author":[{"given":"Jes\u00fas","family":"Borrego","sequence":"first","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3849-6219","authenticated-orcid":false,"given":"Muhammad Umair","family":"Naseem","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Al Nasar Ahmed","family":"Sehgal","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7113-1794","authenticated-orcid":false,"given":"Lipsa Rani","family":"Panda","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4284-6640","authenticated-orcid":false,"given":"Kashmala","family":"Shakeel","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0172-2393","authenticated-orcid":false,"given":"Attila","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, Institute of Chemistry, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, Institute of Chemistry, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1892-6840","authenticated-orcid":false,"given":"Zoltan","family":"Varga","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6227-3301","authenticated-orcid":false,"given":"Gyorgy","family":"Panyi","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"re15","DOI":"10.1126\/stke.2532004re15","article-title":"The VGL-chanome: A protein superfamily specialized for electrical signaling and ionic homeostasis","volume":"2004","author":"Yu","year":"2004","journal-title":"Sci. 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