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This approach was based on a common pharmacophore deduced from sequence and secondary structural homology of 2 Na\n                    <jats:sub>V<\/jats:sub>\n                    inhibitors:\n                    <jats:italic>Conus kinoshitai<\/jats:italic>\n                    toxin IIIA, a 14 residue cone snail peptide with 3 disulfide bonds, and\n                    <jats:italic>Phoneutria nigriventer<\/jats:italic>\n                    toxin 1, a 78 residue spider toxin with 7 disulfide bonds. As with the parent peptides, this novel Na\n                    <jats:sub>V<\/jats:sub>\n                    channel inhibitor was active on Na\n                    <jats:sub>V<\/jats:sub>\n                    1.2. Through the generation of 3 series of peptide mutants, we investigated the role of key residues and cyclization and their influence on Na\n                    <jats:sub>V<\/jats:sub>\n                    inhibition and subtype selectivity. Cyclic PnCS1, a 10 residue peptide cyclized\n                    <jats:italic>via<\/jats:italic>\n                    a disulfide bond, exhibited increased inhibitory activity toward therapeutically relevant Na\n                    <jats:sub>V<\/jats:sub>\n                    channel subtypes, including Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 and Na\n                    <jats:sub>V<\/jats:sub>\n                    1.9, while displaying remarkable serum stability. These peptides represent the first and the smallest cyclic peptide Na\n                    <jats:sub>V<\/jats:sub>\n                    modulators to date and are promising templates for the development of toxin\u2010based therapeutic agents.\u2014Peigneur, S., Cheneval, O., Maiti, M., Leipold, E., Heinemann, S. H., Lescrinier, E., Herdewijn, P., De Lima, M. E., Craik, D. J., Schroeder, C. I., Tytgat, J. Where cone snails and spiders meet: design of small cyclic sodium\u2010channel inhibitors. FASEB J. 33, 3693\u20133703 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801909r","type":"journal-article","created":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T23:24:28Z","timestamp":1543879468000},"page":"3693-3703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Where cone snails and spiders meet: design of small cyclic sodium\u2010channel inhibitors"],"prefix":"10.1096","volume":"33","author":[{"given":"Steve","family":"Peigneur","sequence":"first","affiliation":[{"name":"Toxicology and Pharmacology Katholieke Universiteit (KU) Leuven  Campus Gasthuisberg Leuven Belgium"},{"name":"Department de Bioqu\u00edmica e Imunologia Laborat\u00f3rio de Venenos e Toxinas Animais Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais  Belo-Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Cheneval","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohitosh","family":"Maiti","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry Rega Institute for Medical Research KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Leipold","sequence":"additional","affiliation":[{"name":"Department of Biophysics Center for Molecular Biomedicine Jena University Hospital Friedrich Schiller University Jena  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H.","family":"Heinemann","sequence":"additional","affiliation":[{"name":"Department of Biophysics Center for Molecular Biomedicine Jena University Hospital Friedrich Schiller University Jena  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline","family":"Lescrinier","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry Rega Institute for Medical Research KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piet","family":"Herdewijn","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry Rega Institute for Medical Research KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"De Lima","sequence":"additional","affiliation":[{"name":"Department de Bioqu\u00edmica e Imunologia Laborat\u00f3rio de Venenos e Toxinas Animais Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais  Belo-Horizonte Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Biomedicina e Medicina Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte Grupo Santa Casa de Belo Horizonte  Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Craik","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina I.","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tytgat","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology Katholieke Universiteit (KU) Leuven  Campus Gasthuisberg Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.24380"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/19336950.2015.1031937","article-title":"Gating pore currents, a new pathological mechanism underlying cardiac arrhythmias associated with dilated cardiomyopathy","volume":"9","author":"Moreau A.","year":"2015","journal-title":"Channels (Austin)"},{"key":"e_1_2_8_4_1","first-page":"261","article-title":"Venoms, toxins and derivatives from the Brazilian fauna: valuable sources for drug discovery","volume":"67","author":"De Marco Almeida F.","year":"2015","journal-title":"Sheng Li Xue Bao"},{"key":"e_1_2_8_5_1","first-page":"1","volume-title":"Spider Venoms","author":"De Lima M. 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