{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:45:12Z","timestamp":1784771112592,"version":"3.55.0"},"reference-count":37,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,1,1]]},"abstract":"<jats:p>OSK1 (\u03b1-KTx3.7) is a 38-residue toxin cross-linked by three disulphide bridges that was initially isolated from the venom of the Asian scorpion Orthochirus scrobiculosus. OSK1 and several structural analogues were produced by solid-phase chemical synthesis, and were tested for lethality in mice and for their efficacy in blocking a series of 14 voltage-gated and Ca2+-activated K+ channels in vitro. In the present paper, we report that OSK1 is lethal in mice by intracerebroventricular injection, with a LD50 (50% lethal dose) value of 2\u00a0\u03bcg\/kg. OSK1 blocks Kv1.1, Kv1.2, Kv1.3 channels potently and KCa3.1 channel moderately, with IC50 values of 0.6, 5.4, 0.014 and 225\u00a0nM respectively. Structural analogues of OSK1, in which we mutated positions 16 (Glu16\u2192Lys) and\/or 20 (Lys20\u2192Asp) to amino acid residues that are conserved in all other members of the \u03b1-KTx3 toxin family except OSK1, were also produced and tested. Among the OSK1 analogues, [K16,D20]-OSK1 (OSK1 with Glu16\u2192Lys and Lys20\u2192Asp mutations) shows an increased potency on Kv1.3 channel, with an IC50 value of 0.003\u00a0nM, without loss of activity on KCa3.1 channel. These data suggest that OSK1 or [K16,D20]-OSK1 could serve as leads for the design and production of new immunosuppressive drugs.<\/jats:p>","DOI":"10.1042\/bj20041379","type":"journal-article","created":{"date-parts":[[2004,12,15]],"date-time":"2004-12-15T12:10:58Z","timestamp":1103112658000},"page":"95-104","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["K+ channel types targeted by synthetic OSK1, a toxin from<i>Orthochirus scrobiculosus<\/i>scorpion venom"],"prefix":"10.1042","volume":"385","author":[{"given":"St\u00e9phanie","family":"MOUHAT","sequence":"first","affiliation":[{"name":"Laboratoire Cellpep S.A., 13-15 Rue Ledru-Rollin, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"VISAN","sequence":"additional","affiliation":[{"name":"Universit\u00e4t Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"ANANTHAKRISHNAN","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Toxicology, University of California, Davis, CA 95616, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"WULFF","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Toxicology, University of California, Davis, CA 95616, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"ANDREOTTI","sequence":"additional","affiliation":[{"name":"Laboratoire Cellpep S.A., 13-15 Rue Ledru-Rollin, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"GRISSMER","sequence":"additional","affiliation":[{"name":"Universit\u00e4t Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"DARBON","sequence":"additional","affiliation":[{"name":"AFMB, CNRS UPR 9039, 31 Chemin Joseph Aiguier, 13402 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"DE\u00a0WAARD","sequence":"additional","affiliation":[{"name":"INSERM U607, CEA, 17 Rue des Martyrs, 38054 Grenoble Cedex 09, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"SABATIER","sequence":"additional","affiliation":[{"name":"Laboratoire Cellpep S.A., 13-15 Rue Ledru-Rollin, 13015 Marseille, France"},{"name":"CNRS FRE 2738, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2004,12,14]]},"reference":[{"key":"2021112214134677900_B1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1021\/bi9614390","article-title":"Three-dimensional structure of toxin from Orthochirus scrobiculosus scorpion venom","volume":"36","author":"Jaravine","year":"1997","journal-title":"Biochemistry"},{"key":"2021112214134677900_B2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1042\/bj20031860","article-title":"Diversity of folds in animal toxins acting on ion channels","volume":"378","author":"Mouhat","year":"2004","journal-title":"Biochem. J."},{"key":"2021112214134677900_B3","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1126\/science.1720574","article-title":"Refined structure of charybdotoxin: common motifs in scorpion toxins and insect defensins","volume":"254","author":"Bontems","year":"1991","journal-title":"Science"},{"key":"2021112214134677900_B4","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/0896-6273(95)90104-3","article-title":"Topology of the pore-region of a K+ channel revealed by the NMR-derived structures of scorpion toxins","volume":"15","author":"Aiyar","year":"1995","journal-title":"Neuron"},{"key":"2021112214134677900_B5","doi-asserted-by":"crossref","first-page":"6834","DOI":"10.1021\/bi00188a012","article-title":"Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom","volume":"33","author":"Garcia","year":"1994","journal-title":"Biochemistry"},{"key":"2021112214134677900_B6","doi-asserted-by":"crossref","first-page":"13473","DOI":"10.1021\/bi971044w","article-title":"Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels","volume":"36","author":"Romi-Lebrun","year":"1997","journal-title":"Biochemistry"},{"key":"2021112214134677900_B7","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0165-6147(99)01398-X","article-title":"A unified nomenclature for short-chain peptides isolated from scorpion venoms: \u03b1-KTx","volume":"20","author":"Tytgat","year":"1999","journal-title":"Trends Physiol. Sci."},{"key":"2021112214134677900_B8","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.toxicon.2004.03.022","article-title":"Current views on scorpion toxins specific for K+ channels","volume":"43","author":"Rodriguez\u00a0de\u00a0la\u00a0Vega","year":"2004","journal-title":"Toxicon"},{"key":"2021112214134677900_B9","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1351\/pac199668112105","article-title":"Structure and function of the potassium channel inhibitor from black scorpion venom","volume":"68","author":"Grishin","year":"1996","journal-title":"Pure Appl. Chem."},{"key":"2021112214134677900_B10","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1126\/science.3961484","article-title":"Solid phase synthesis","volume":"232","author":"Merrifield","year":"1986","journal-title":"Science"},{"key":"2021112214134677900_B11","first-page":"1227","article-title":"Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv 1.1, 1.2, 1.3, 1.5 and 3.1, stably expressed in mammalian cell lines","volume":"45","author":"Grissmer","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"2021112214134677900_B12","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF00656997","article-title":"Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membranes patches","volume":"391","author":"Hamill","year":"1981","journal-title":"Pfl\u00fcgers Arch."},{"key":"2021112214134677900_B13","first-page":"1625","article-title":"Evidence for an internal phenylalkylamine action on the voltage-gated potassium channel Kv1.3","volume":"50","author":"Rauer","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"2021112214134677900_B14","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1042\/bj20030977","article-title":"Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels","volume":"377","author":"Jouirou","year":"2004","journal-title":"Biochem. J."},{"key":"2021112214134677900_B15","doi-asserted-by":"crossref","first-page":"39394","DOI":"10.1074\/jbc.M006810200","article-title":"Maurotoxin versus Pi1\/HsTx1 toxins: Toward new insights in the understanding of their distinct disulfide bridge patterns","volume":"275","author":"Fajloun","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021112214134677900_B16","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1021\/bi00062a005","article-title":"P05, a new leiurotoxin I-like scorpion toxin: synthesis and structure-activity relationships of the \u03b1-amidated analog, a ligand of Ca2+-activated K+ channels with increased affinity","volume":"32","author":"Sabatier","year":"1993","journal-title":"Biochemistry"},{"key":"2021112214134677900_B17","doi-asserted-by":"crossref","first-page":"26302","DOI":"10.1016\/S0021-9258(19)74315-4","article-title":"Synthesis and characterization of kaliotoxin: is the 26\u201332 sequence essential for potassium channel recognition?","volume":"268","author":"Romi","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2021112214134677900_B18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.tips.2004.03.010","article-title":"K+ channels as targets for specific immunomodulation","volume":"25","author":"Chandy","year":"2004","journal-title":"Trends Pharmacol. Sci."},{"key":"2021112214134677900_B19","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1042\/bj3280321","article-title":"A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom","volume":"328","author":"Lebrun","year":"1997","journal-title":"Biochem. J."},{"key":"2021112214134677900_B20","doi-asserted-by":"crossref","first-page":"32697","DOI":"10.1074\/jbc.273.49.32697","article-title":"ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide","volume":"273","author":"Kalman","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021112214134677900_B21","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.1046\/j.1432-1327.2000.01577.x","article-title":"Chemical synthesis and characterization of Pi1, a scorpion toxin from Pandinus imperator active on K+ channels","volume":"267","author":"Fajloun","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"2021112214134677900_B22","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1046\/j.1432-1033.2003.03743.x","article-title":"Synthesis and characterization of Pi4, a scorpion toxin from Pandinus imperator that acts on K+ channels","volume":"270","author":"M'Barek","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"2021112214134677900_B23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S1570-9639(02)00458-2","article-title":"Two novel toxins from the Amazonian scorpion Tityus cambridgei that block Kv1.3 and Shaker B K+ channels with distinctly different affinities","volume":"1601","author":"Batista","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"2021112214134677900_B24","first-page":"15","article-title":"Structure and function of scorpion toxins affecting K+ channels","volume-title":"Perspectives in Drug Discovery and Design: Animal Toxins and Potassium Channels, vol. 15\/16","author":"Possani","year":"1999"},{"key":"2021112214134677900_B25","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/sj.ejhg.5200739","article-title":"Characterisation of the human voltage-gated potassium gene, KCNA7, a candidate gene for inherited cardiac disorders, and its exclusion as cause of progressive familial heart block I (PFHBI)","volume":"10","author":"Bardien-Kruger","year":"2002","journal-title":"Eur. J. Hum. Genet."},{"key":"2021112214134677900_B26","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.4049\/jimmunol.158.11.5120","article-title":"Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo","volume":"158","author":"Koo","year":"1997","journal-title":"J. Immunol."},{"key":"2021112214134677900_B27","doi-asserted-by":"crossref","first-page":"936","DOI":"10.4049\/jimmunol.166.2.936","article-title":"Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation","volume":"166","author":"Beeton","year":"2001","journal-title":"J. Immunol."},{"key":"2021112214134677900_B28","doi-asserted-by":"crossref","first-page":"13942","DOI":"10.1073\/pnas.241497298","article-title":"Selective blockade of T lymphocyte K+ channels ameliorates experimental encephalomyelitis, a model for multiple sclerosis","volume":"98","author":"Beeton","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112214134677900_B29","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1172\/JCI16921","article-title":"The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS","volume":"111","author":"Wulff","year":"2003","journal-title":"J. Clin. Invest."},{"key":"2021112214134677900_B30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.imlet.2003.11.020","article-title":"Ion channels and lymphocyte activation","volume":"92","author":"Panyi","year":"2004","journal-title":"Immunol. Lett."},{"key":"2021112214134677900_B31","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S0165-6147(03)00080-4","article-title":"Novel interactions between K+ channels and scorpion toxins","volume":"24","author":"Rodriguez\u00a0de\u00a0la\u00a0Vega","year":"2003","journal-title":"Trends Pharmacol. Sci."},{"key":"2021112214134677900_B32","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.toxicon.2003.12.011","article-title":"Block of maurotoxin and charybdotoxin on human intermediate-conductance calcium-activated potassium channels (hIKCa1)","volume":"43","author":"Visan","year":"2004","journal-title":"Toxicon"},{"key":"2021112214134677900_B33","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1124\/mol.104.002774","article-title":"Mapping of maurotoxin binding sites on hKv1.2, hKv1.3 and hIKCa1 channels","volume":"66","author":"Visan","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"2021112214134677900_B34","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1529\/biophysj.103.039461","article-title":"Computational simulations of interactions of scorpion toxins with the voltage-gated potassium ion channel","volume":"86","author":"Yu","year":"2004","journal-title":"Biophys. J."},{"key":"2021112214134677900_B35","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1124\/mol.63.2.409","article-title":"Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels","volume":"63","author":"Castle","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"2021112214134677900_B36","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1074\/jbc.275.2.1201","article-title":"Structure-guided transformation of charybdotoxin yields an analog that selectively targets Ca2+-activated over voltage-gated K+ channels","volume":"275","author":"Rauer","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021112214134677900_B37","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1042\/bj20030115","article-title":"The \u2018functional\u2019 dyad of scorpion toxin Pi1 is not itself a prerequisite for toxin binding to the voltage-gated Kv1.2 potassium channels","volume":"377","author":"Mouhat","year":"2004","journal-title":"Biochem. J."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/385\/1\/95\/717268\/bj3850095.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/385\/1\/95\/717268\/bj3850095.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T22:20:03Z","timestamp":1682893203000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/385\/1\/95\/44212\/K-channel-types-targeted-by-synthetic-OSK1-a-toxin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,14]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,1,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20041379","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,14]]}}}