Abstract
Synthetic glycopeptide dendrimers composed of a branched oligopeptide tree structure appended with glycosidic groups at its multiple N-termini were investigated for binding to the Pseudomonas aeruginosa lectins LecB and LecA. These lectins are partly responsible for the formation of antibiotic resistant biofilms in the human pathogenic bacterium P. aeruginosa, which causes lethal airway infections in immune-compromised and cystic fibrosis patients. Glycopeptide dendrimers with high affinity to the lectins were identified by screening of combinatorial libraries. Several of these dendrimers, in particular the LecB specific glycopeptide dendrimers FD2 and D-FD2 and the LecA specific glycopeptide dendrimers GalAG2 and GalBG2, also efficiently block P. aeruginosa biofilm formation and induce biofilm dispersal in vitro. Structure-activity relationship and structural studies are reviewed, in particular the observation that multivalency is essential to the anti-biofilm effect in these dendrimers.
Highlights
The spread of antibiotic resistant bacteria is one of the most pressing problems in human health today
Appending the peptide arms with a glycosidic ligand within a combinatorial library set-up led to the discovery of the fucosylated peptide dendrimer FD2,19 a tetravalent ligand binding to the fucose-specific lectin LecB, and the related galactosylated dendrimers GalAG2 and GalBG2, which target the galactose specific lectin LecA
We recently introduced a new class of dendrimers assembled from amino acid building blocks by solid-phase peptide synthesis.[22]
Summary
The spread of antibiotic resistant bacteria is one of the most pressing problems in human health today. Jean-Louis Reymond is a Professor of Chemistry and Chemical Biology at the University of Berne, Switzerland He studied chemistry and biochemistry at the ETH Zurich and obtained his PhD in 1989 at the University of Lausanne in the area of natural products synthesis. Dr Jean-Louis Reymond at the University of Berne (Switzerland) Her current research interests are the synthesis and analysis of glycopeptide dendrimers as Pseudomonas aeruginosa biofilm inhibitors. Appending the peptide arms with a glycosidic ligand within a combinatorial library set-up led to the discovery of the fucosylated peptide dendrimer FD2,19 a tetravalent ligand binding to the fucose-specific lectin LecB, and the related galactosylated dendrimers GalAG2 and GalBG2, which target the galactose specific lectin LecA These dendrimers are potent P. aeruginosa biofilm inhibitors (Fig. 1).[20,21] Structure–activity relationship studies show that multivalency is crucial for biofilm inhibition and dispersal with these ligands
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