{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:04:05Z","timestamp":1775610245331,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,21]],"date-time":"2015-03-21T00:00:00Z","timestamp":1426896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003958","name":"Dutch Technology Foundation (STW)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003958","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Applied Science Division of the Netherlands Organization for Scientific Research (NWO)"},{"name":"Technology Program of the Ministry of Economic Affairs"},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology (COST)","doi-asserted-by":"crossref","award":["CM1102 MultiGlycoNano"],"award-info":[{"award-number":["CM1102 MultiGlycoNano"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistryOpen"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The five B\u2010subunits (CTB<jats:sub>5<\/jats:sub>) of the <jats:italic>Vibrio cholerae<\/jats:italic> (cholera) toxin can bind to the intestinal cell surface so the entire AB<jats:sub>5<\/jats:sub> toxin can enter the cell. Simultaneous binding can occur on more than one of the monosialotetrahexosylganglioside (GM1) units present on the cell surface. Such simultaneous binding arising from the toxins multivalency is believed to enhance its affinity. Thus, blocking the initial attachment of the toxin to the cell surface using inhibitors with GM1 subunits has the potential to stop the disease. Previously we showed that tetravalent GM1 molecules were sub\u2010nanomolar inhibitors of CTB<jats:sub>5<\/jats:sub>. In this study, we synthesized a pentavalent version and compared the binding and potency of penta\u2010 and tetravalent cholera toxin inhibitors, based on the same scaffold, for the first time. The pentavalent geometry did not yield major benefits over the tetravalent species, but it was still a strong inhibitor, and no major steric clashes occurred when binding the toxin. Thus, systems which can adopt more geometries, such as those described here, can be equally potent, and this may possibly be due to their ability to form higher\u2010order structures or simply due to more statistical options for binding.<\/jats:p>","DOI":"10.1002\/open.201500006","type":"journal-article","created":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T12:24:05Z","timestamp":1427199845000},"page":"471-477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tetra\u2010 versus Pentavalent Inhibitors of Cholera Toxin"],"prefix":"10.1002","volume":"4","author":[{"given":"Ou","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry and Chemical Biology Utrecht University  P.O. Box 80082 3508 TB Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliaksei V.","family":"Pukin","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Chemical Biology Utrecht University  P.O. Box 80082 3508 TB Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. C. Quarles","family":"van\u2005Ufford","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Chemical Biology Utrecht University  P.O. Box 80082 3508 TB Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R.","family":"Branson","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Chemical Biology Utrecht University  P.O. Box 80082 3508 TB Utrecht The Netherlands"},{"name":"School of Chemistry and Astbury Centre for Structural Molecular Biology University of Leeds  Leeds LS2 9JT United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique M. E.","family":"Thies\u2010Weesie","sequence":"additional","affiliation":[{"name":"Van \u2018t Hoff Laboratory for Physical and Colloid Chemistry Debye Institute for Nanomaterials Science Utrecht University  Padualaan 8 3584 CH Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Bruce","family":"Turnbull","sequence":"additional","affiliation":[{"name":"School of Chemistry and Astbury Centre for Structural Molecular Biology University of Leeds  Leeds LS2 9JT United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerben M.","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology Faculty of Veterinary Medicine Utrecht University  PO Box 80.165 3508 TD Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland J.","family":"Pieters","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Chemical Biology Utrecht University  P.O. 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