Non-Carbohydrate Glycomimetics as Inhibitors of Calcium(II)-Binding Lectins.
PAINS
carbohydrates
catechol
glycomimetic
lectin
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
06 04 2021
06 04 2021
Historique:
received:
30
09
2020
pubmed:
15
12
2020
medline:
23
7
2021
entrez:
14
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33314528
doi: 10.1002/anie.202013217
pmc: PMC8048816
doi:
Substances chimiques
Adhesins, Bacterial
0
Anti-Bacterial Agents
0
Catechols
0
Glycosides
0
LecA protein, bacteria
0
catechol
LF3AJ089DQ
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8104-8114Informations de copyright
© 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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