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

摘要: 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 binding to natural saccharides might provide new opportunities for treatment. Here 8-fold (G3) 16-fold (G4) galactosylated analogs GalAG2, a tetravalent G2 glycopeptide dendrimer ligand P. aeruginosa biofilm inhibitor, were obtained convergent chloroacetyl thioether (ClAc) ligation between 4-fold or chloroacetylated cores digalactosylated dendritic arms. Hemagglutination inhibition, isothermal titration calorimetry inhibition assays showed G3 dendrimers bind slightly better than their parent induce complete dispersal biofilms, while G4 show reduced no inhibition. A model accounting observed saturation galactosyl groups sites is proposed based on crystal structure complex.