The Parkinson's Disease Drug Tolcapone and Analogues are Potent Glycomimetic Lectin Inhibitors of Pseudomonas aeruginosa LecA.

ABSTRACT: The notorious pathogen Pseudomonas aeruginosa relies on the lectin LecA for host cell adhesion, invasion, and biofilm formation. Motivated by the pressing need for new anti-infective therapies caused by antimicrobial resistance, inhibitors of LecA are under investigation. Complementary to the use of carbohydrate-based inhibitors, we have previously identified catechols as weak but specific ligands of LecA, constituting a novel class of non-carbohydrate glycomimetics. By growing the initial millimolar fragment hits, we identified Tolcapone as a promising compound. To gain insight into the structure-activity relationship (SAR) of catechols as LecA binders, more than 3,200 compounds of the Roche in-house library were experimentally screened in a competitive binding assay at three concentratio

SUBMITTER: Leusmann S 

PROVIDER: S-EPMC12684298 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature