{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:44:28Z","timestamp":1793817868544,"version":"4.6.1"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,12,24]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>G protein-coupled receptors (GPCRs) are promising drug targets: &gt;30% of the currently marketed drugs elicit their actions by binding to these transmembrane receptors. However, only \u223c10% of all GPCRs are targeted by approved drugs. Resorting to plant-derived compounds catalogued by ethnopharmacological analyses may increase this repertoire. We provide a proof of concept by analyzing the uterotonic action of an herbal remedy used in traditional African medicine. We identified cyclic peptides, investigated the molecular mechanisms underlying their uterotonic activity, and report an oxytocic plant peptide that modulates the human oxytocin\/vasopressin receptors. This naturally occurring peptide served as a template for the design of an oxytocin-like nonapeptide with enhanced receptor selectivity, highlighting the potential of cyclotides for the discovery of peptide-based GPCR ligands.<\/jats:p>","DOI":"10.1073\/pnas.1311183110","type":"journal-article","created":{"date-parts":[[2013,11,18]],"date-time":"2013-11-18T23:49:39Z","timestamp":1384818579000},"page":"21183-21188","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":151,"title":["Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design"],"prefix":"10.1073","volume":"110","author":[{"given":"Johannes","family":"Koehbach","sequence":"first","affiliation":[{"name":"Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"National Centre for Biomedical Engineering Science and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Muttenthaler","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Miazzo","sequence":"additional","affiliation":[{"name":"Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muharrem","family":"Akcan","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alysha G.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norelle L.","family":"Daly","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia;"},{"name":"School of Pharmacy and Molecular Sciences, Centre for Biodiscovery and Molecular Development of Therapeutics, Queensland Tropical Health Alliance, James Cook University, Cairns, QLD 4878, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peta J.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Arrowsmith","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunithi","family":"Gunasekera","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry J.","family":"Smith","sequence":"additional","affiliation":[{"name":"National Centre for Biomedical Engineering Science and"},{"name":"The School of Natural Sciences, National University of Ireland, Galway, Ireland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Wray","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"G\u00f6ransson","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip E.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Departments of Chemistry and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Craik","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Freissmuth","sequence":"additional","affiliation":[{"name":"Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian W.","family":"Gruber","sequence":"additional","affiliation":[{"name":"Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,11,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1006\/jmbi.1999.3383","article-title":"Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif","volume":"294","author":"Craik DJ","year":"1999","unstructured":"DJ Craik, NL Daly, T Bond, C Waine, Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. 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