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Multivalency effects on Pseudomonas aeruginosa biofilm inhibition and dispersal by glycopeptide dendrimers targeting lectin LecA

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Bergmann Myriam, Michaud Gaëlle, Visini Ricardo, Jin Xian, Gillon Emilie, Stocker Achim, Imbertry Anne, Darbre Tamis, Reymond Jean-Louis,
Project A Chemical Space Approach to Bioactive Peptides
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Original article (peer-reviewed)

Journal Organic & Biomolecular Chemistry
Volume (Issue) 14
Page(s) 138 - 142
Title of proceedings Organic & Biomolecular Chemistry
DOI 10.1039/c5ob01682g

Open Access


The galactose specific lectin LecA partly mediates the formation of antibiotic resistant biofilms by Pseudomonas aeruginosa, an opportunistic pathogen causing lethal airways infections in immunocompromised and cystic fibrosis patients, suggesting that preventing LecA binding to natural saccharides might provide new opportunities for treatment. Here 8-fold (G3) and 16-fold (G4) galactosylated analogs of GalAG2, a tetravalent G2 glycopeptide dendrimer LecA ligand and P. aeruginosa biofilm inhibitor, were obtained by convergent chloroacetyl thioether (ClAc) ligation between 4-fold or 8-fold chloroacetylated dendrimer cores and digalactosylated dendritic arms. Hemagglutination inhibition, isothermal titration calorimetry and biofilm inhibition assays showed that G3 dendrimers bind LecA slightly better than their parent G2 dendrimers and induce complete biofilm inhibition and dispersal of P. aeruginosa biofilms, while G4 dendrimers show reduced binding and no biofilm inhibition. A binding model accounting for the observed saturation of glycopeptide dendrimer galactosyl groups and LecA binding sites is proposed based on the crystal structure of a G3 dendrimer LecA complex.