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dc.contributor.authorKuhaudomlarp, Sakonwan
dc.contributor.authorSiebs, Eike
dc.contributor.authorShanina, Elena
dc.contributor.authorTopin, Jérémie
dc.contributor.authorJoachim, Ines
dc.contributor.authorda Silva Figueiredo Celestino Gomes, Priscila
dc.contributor.authorVarrot, Annabelle
dc.contributor.authorRognan, Didier
dc.contributor.authorRademacher, Christoph
dc.contributor.authorImberty, Anne
dc.contributor.authorTitz, Alexander
dc.date.accessioned2021-04-27T11:40:29Z
dc.date.available2021-04-27T11:40:29Z
dc.date.issued2021-03-03
dc.identifier.citationAngew Chem Int Ed Engl. 2021 Apr 6;60(15):8104-8114. doi: 10.1002/anie.202013217. Epub 2021 Mar 3.en_US
dc.identifier.pmid33314528
dc.identifier.doi10.1002/anie.202013217
dc.identifier.urihttp://hdl.handle.net/10033/622844
dc.description.abstractBecause of the antimicrobial resistance crisis, lectins are considered novel drug targets. Pseudomonas aeruginosa utilizes LecA and LecB in the infection process. Inhibition of both lectins with carbohydrate-derived molecules can reduce biofilm formation to restore antimicrobial susceptibility. Here, we focused on non-carbohydrate inhibitors for LecA to explore new avenues for lectin inhibition. From a screening cascade we obtained one experimentally confirmed hit, a catechol, belonging to the well-known PAINS compounds. Rigorous analyses validated electron-deficient catechols as millimolar LecA inhibitors. The first co-crystal structure of a non-carbohydrate inhibitor in complex with a bacterial lectin clearly demonstrates the catechol mimicking the binding of natural glycosides with LecA. Importantly, catechol 3 is the first non-carbohydrate lectin ligand that binds bacterial and mammalian calcium(II)-binding lectins, giving rise to this fundamentally new class of glycomimetics.en_US
dc.language.isoenen_US
dc.publisherWiley-VCHen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectPAINSen_US
dc.subjectcarbohydratesen_US
dc.subjectcatecholen_US
dc.subjectglycomimeticen_US
dc.subjectlectinen_US
dc.titleNon-Carbohydrate Glycomimetics as Inhibitors of Calcium(II)-Binding Lectins.en_US
dc.typeArticleen_US
dc.identifier.eissn1521-3773
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalAngewandte Chemie (International ed. in English)en_US
dc.source.volume60
dc.source.issue15
dc.source.beginpage8104
dc.source.endpage8114
refterms.dateFOA2021-04-27T11:40:29Z
dc.source.journaltitleAngewandte Chemie (International ed. in English)
dc.source.countryGermany


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International