Non-Carbohydrate Glycomimetics as Inhibitors of Calcium(II)-Binding Lectins.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
da Silva Figueiredo Celestino Gomes, Priscila
MetadataShow full item record
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.
CitationAngew Chem Int Ed Engl. 2021 Apr 6;60(15):8104-8114. doi: 10.1002/anie.202013217. Epub 2021 Mar 3.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
The following license files are associated with this item:
- Creative Commons
- Genomic Rearrangements and Functional Diversification of lecA and lecB Lectin-Coding Regions Impacting the Efficacy of Glycomimetics Directed against Pseudomonas aeruginosa.
- Authors: Boukerb AM, Decor A, Ribun S, Tabaroni R, Rousset A, Commin L, Buff S, Doléans-Jordheim A, Vidal S, Varrot A, Imberty A, Cournoyer B
- Issue date: 2016
- Covalent Lectin Inhibition and Application in Bacterial Biofilm Imaging.
- Authors: Wagner S, Hauck D, Hoffmann M, Sommer R, Joachim I, Müller R, Imberty A, Varrot A, Titz A
- Issue date: 2017 Dec 22
- Cinnamide Derivatives of d-Mannose as Inhibitors of the Bacterial Virulence Factor LecB from Pseudomonas aeruginosa.
- Authors: Sommer R, Hauck D, Varrot A, Wagner S, Audfray A, Prestel A, Möller HM, Imberty A, Titz A
- Issue date: 2015 Dec
- Role of LecA and LecB lectins in Pseudomonas aeruginosa-induced lung injury and effect of carbohydrate ligands.
- Authors: Chemani C, Imberty A, de Bentzmann S, Pierre M, Wimmerová M, Guery BP, Faure K
- Issue date: 2009 May
- Secondary sugar binding site identified for LecA lectin from Pseudomonas aeruginosa.
- Authors: Blanchard B, Imberty A, Varrot A
- Issue date: 2014 Jun