Non-Carbohydrate Glycomimetics as Inhibitors of Calcium(II)-Binding Lectins.
dc.contributor.author | Kuhaudomlarp, Sakonwan | |
dc.contributor.author | Siebs, Eike | |
dc.contributor.author | Shanina, Elena | |
dc.contributor.author | Topin, Jérémie | |
dc.contributor.author | Joachim, Ines | |
dc.contributor.author | da Silva Figueiredo Celestino Gomes, Priscila | |
dc.contributor.author | Varrot, Annabelle | |
dc.contributor.author | Rognan, Didier | |
dc.contributor.author | Rademacher, Christoph | |
dc.contributor.author | Imberty, Anne | |
dc.contributor.author | Titz, Alexander | |
dc.date.accessioned | 2021-04-27T11:40:29Z | |
dc.date.available | 2021-04-27T11:40:29Z | |
dc.date.issued | 2021-03-03 | |
dc.identifier.citation | Angew Chem Int Ed Engl. 2021 Apr 6;60(15):8104-8114. doi: 10.1002/anie.202013217. Epub 2021 Mar 3. | en_US |
dc.identifier.pmid | 33314528 | |
dc.identifier.doi | 10.1002/anie.202013217 | |
dc.identifier.uri | http://hdl.handle.net/10033/622844 | |
dc.description.abstract | Because 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.iso | en | en_US |
dc.publisher | Wiley-VCH | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | PAINS | en_US |
dc.subject | carbohydrates | en_US |
dc.subject | catechol | en_US |
dc.subject | glycomimetic | en_US |
dc.subject | lectin | en_US |
dc.title | Non-Carbohydrate Glycomimetics as Inhibitors of Calcium(II)-Binding Lectins. | en_US |
dc.type | Article | en_US |
dc.identifier.eissn | 1521-3773 | |
dc.contributor.department | HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. | en_US |
dc.identifier.journal | Angewandte Chemie (International ed. in English) | en_US |
dc.source.volume | 60 | |
dc.source.issue | 15 | |
dc.source.beginpage | 8104 | |
dc.source.endpage | 8114 | |
refterms.dateFOA | 2021-04-27T11:40:29Z | |
dc.source.journaltitle | Angewandte Chemie (International ed. in English) | |
dc.source.country | Germany |