{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T05:50:57Z","timestamp":1769579457189,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2013,4,8]],"date-time":"2013-04-08T00:00:00Z","timestamp":1365379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>A novel peptide, RsXXIVA, was isolated from the venom duct of Conus regularis, a worm-hunting species collected in the Sea of Cortez, M\u00e9xico. Its primary structure was determined by mass spectrometry and confirmed by automated Edman degradation. This conotoxin contains 40 amino acids and exhibits a novel arrangement of eight cysteine residues (C-C-C-C-CC-CC). Surprisingly, two loops of the novel peptide are highly identical to the amino acids sequence of \u03c9-MVIIA. The total length and disulfide pairing of both peptides are quite different, although the two most important residues for the described function of \u03c9-MVIIA (Lys2 and Tyr13) are also present in the peptide reported here. Electrophysiological analysis using superior cervical ganglion (SCG) neurons indicates that RsXXIVA inhibits CaV2.2 channel current in a dose-dependent manner with an EC50 of 2.8 \u03bcM, whose effect is partially reversed after washing. Furthermore, RsXXIVA was tested in hot-plate assays to measure the potential anti-nociceptive effect to an acute thermal stimulus, showing an analgesic effect in acute thermal pain at 30 and 45 min post-injection. Also, the toxin shows an anti-nociceptive effect in a formalin chronic pain test. However, the low affinity for CaV2.2 suggests that the primary target of the peptide could be different from that of \u03c9-MVIIA.<\/jats:p>","DOI":"10.3390\/md11041188","type":"journal-article","created":{"date-parts":[[2013,4,8]],"date-time":"2013-04-08T12:01:31Z","timestamp":1365422491000},"page":"1188-1202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A Conus regularis Conotoxin with a Novel Eight-Cysteine Framework Inhibits CaV2.2 Channels and Displays an  Anti-Nociceptive Activity"],"prefix":"10.3390","volume":"11","author":[{"given":"Johanna","family":"Bern\u00e1ldez","sequence":"first","affiliation":[{"name":"Molecular Immunology and Biotoxins Laboratory, Marine Biotechnology Department, Scientific Research and High Education Center from Ensenada (CICESE), Carretera Ensenada-Tijuana #3918, Zona Playitas, Ensenada 22860, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Rom\u00e1n-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Chemistry Biomacromolecules Department, Chemistry Institute, National Autonomous University of Mexico, Av. Universidad 3000, Ciudad Universitaria, PO BOX 70-213, D.F. 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Biotoxins Laboratory, Marine Biotechnology Department, Scientific Research and High Education Center from Ensenada (CICESE), Carretera Ensenada-Tijuana #3918, Zona Playitas, Ensenada 22860, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0363-0310","authenticated-orcid":false,"given":"Samanta","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Biotoxins Laboratory, Marine Biotechnology Department, Scientific Research and High Education Center from Ensenada (CICESE), Carretera Ensenada-Tijuana #3918, Zona Playitas, Ensenada 22860, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Vivas","sequence":"additional","affiliation":[{"name":"Physiology Department, Medicine Faculty, National Autonomous University of Mexico, Av. Universidad 3000, Ciudad Universitaria, PO BOX 70-250, D.F. 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Arenas","sequence":"additional","affiliation":[{"name":"Physiology Department, Medicine Faculty, National Autonomous University of Mexico, Av. Universidad 3000, Ciudad Universitaria, PO BOX 70-250, D.F. 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9513-1622","authenticated-orcid":false,"given":"Gerardo","family":"Corzo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Bioprocesses, National Autonomous University of Mexico, Av. Universidad 2001, C.P. 510-3, Cuernavaca 61500, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-4770","authenticated-orcid":false,"given":"Roberto","family":"Arregu\u00edn","sequence":"additional","affiliation":[{"name":"Chemistry Biomacromolecules Department, Chemistry Institute, National Autonomous University of Mexico, Av. Universidad 3000, Ciudad Universitaria, PO BOX 70-213, D.F. 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Physiology Department, Medicine Faculty, National Autonomous University of Mexico, Av. Universidad 3000, Ciudad Universitaria, PO BOX 70-250, D.F. 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-2661","authenticated-orcid":false,"given":"Lourival","family":"Possani","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Bioprocesses, National Autonomous University of Mexico, Av. Universidad 2001, C.P. 510-3, Cuernavaca 61500, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4022-7405","authenticated-orcid":false,"given":"Alexei","family":"Licea","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Biotoxins Laboratory, Marine Biotechnology Department, Scientific Research and High Education Center from Ensenada (CICESE), Carretera Ensenada-Tijuana #3918, Zona Playitas, Ensenada 22860, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.2174\/138161208785777469","article-title":"Conus Venoms\u2014A rich source of peptide-based therapeutics","volume":"14","author":"Han","year":"2008","journal-title":"Curr. Pharm. 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Interact."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/bioinformatics\/btm596","article-title":"ConoServer, a database for conopeptide sequences and structures","volume":"24","author":"Kass","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.toxicon.2010.09.015","article-title":"Electrophysiological characterization of a novel small peptide from the venom of Conus californicus that targets voltage-gated neuronal Ca2+ channels","volume":"57","author":"Licea","year":"2011","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9163","DOI":"10.1523\/JNEUROSCI.18-22-09163.1998","article-title":"G-Protein \u03b2-subunit specificity in the fast membrane-delimited inhibition of Ca2+ channels","volume":"18","author":"Garcia","year":"1998","journal-title":"J. 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