Non-Carbohydrate Glycomimetics as Inhibitors of Calcium(II)-Binding Lectins.
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Authors
Kuhaudomlarp, SakonwanSiebs, Eike
Shanina, Elena
Topin, Jérémie
Joachim, Ines
da Silva Figueiredo Celestino Gomes, Priscila
Varrot, Annabelle
Rognan, Didier
Rademacher, Christoph
Imberty, Anne
Titz, Alexander

Issue Date
2021-03-03
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Show full item recordAbstract
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.Citation
Angew Chem Int Ed Engl. 2021 Apr 6;60(15):8104-8114. doi: 10.1002/anie.202013217. Epub 2021 Mar 3.Affiliation
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.Publisher
Wiley-VCHPubMed ID
33314528Type
ArticleLanguage
enEISSN
1521-3773ae974a485f413a2113503eed53cd6c53
10.1002/anie.202013217
Scopus Count
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