{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:37:20Z","timestamp":1791229040758,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,4,2]],"date-time":"2009-04-02T00:00:00Z","timestamp":1238630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2009,5,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Sweet medicine<\/jats:bold>: Multimeric glycoconjugates with valencies ranging from one to four were synthesized by click chemistry. Unprecedented adhesion inhibitions of piliated <jats:italic>E.\u2005coli<\/jats:italic> to human bladder cells were recorded with the multimers; a tetravalent derivative showed inhibitory concentrations 6000\u2010 and 64\u2010fold lower than mannose and heptyl \u03b1\u2010<jats:sc>D<\/jats:sc>\u2010mannoside, respectively.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/gif\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/mcontent.gif\"><jats:alt-text>magnified image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p><jats:italic>Urinary tract infections caused by uropathogenic<\/jats:italic> Escherichia\u2005coli <jats:italic>presents a serious communal and nosocomial health problem initiated by bacterial adhesion to the bladder cells.<\/jats:italic> E.\u2005coli <jats:italic>expresses fimbriae with a mannose\u2010binding adhesin, FimH, at the tip. Heptyl \u03b1\u2010<jats:sc>D<\/jats:sc>\u2010mannoside (HM) is a nanomolar inhibitor of this lectin, preventing adhesion of type 1\u2010piliated<\/jats:italic> E.\u2005coli <jats:italic>and reducing bacteria levels in a murine cystitis model. Herein, we described the synthesis of multimeric heptyl\u2010mannosides with valencies ranging from one to four by copper\u2010catalyzed azide alkyne cycloaddition (CuAAC). Biological evaluation of the multivalent compounds revealed an increase in potency compared to HM. Inhibition of bladder cell binding highlighted a promising tetravalent derivative with inhibitory concentrations 6000\u2010 and 64\u2010fold lower than mannose and HM respectively.<\/jats:italic><\/jats:p>","DOI":"10.1002\/cmdc.200900034","type":"journal-article","created":{"date-parts":[[2009,4,2]],"date-time":"2009-04-02T09:26:09Z","timestamp":1238664369000},"page":"749-755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Synthetic Multimeric Heptyl Mannosides as Potent Antiadhesives of Uropathogenic <i>Escherichia coli<\/i>"],"prefix":"10.1002","volume":"4","author":[{"given":"S\u00e9bastien\u2005G.","family":"Gouin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adinda","family":"Wellens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bouckaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Kovensky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,5,4]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2007.06.011"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308125100"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084550"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04415.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002040"},{"key":"e_1_2_6_6_2","unstructured":"\u00a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo071248a"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1039\/B610741A"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo052045u"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1039\/b708227d"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carres.2006.04.028"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200300719"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1039\/B610741A"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/b800598b"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetasy.2004.11.014"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.20089"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200502794"},{"key":"e_1_2_6_17_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200502794"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200800700"},{"key":"e_1_2_6_19_2","unstructured":"To date the glycoconjugate with the highest binding affinity for FimH recorded by SPR is a tetrameric compound (Kd=0.45\u2005nM) developed by R. 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