The opportunistic bacterium Pseudomonas aeruginosa, often exhibiting multiresistance against conventional antibiotics, expresses the lectin LecB that is suspected to be an important factor during biofilm formation via interactions with cell-surface presented carbohydrate ligands such as the blood group antigens. Therefore, carbohydrate-based ligands interfering with LecB binding have the potential to lead to new anti-biofilm and anti-adhesion therapies. This study explores in vitro binding potencies of glycomimetic ligands containing up to six α-l-fucose ligands on a monodisperse, sequence-controlled oligoamide scaffold interacting with LecB. Surface plasmon resonance (SPR) and a modified enzyme-linked lectin assay (mELLA) revealed an increasing affinity to LecB with increasing fucose valency. Furthermore, fucosylated glycooligomers were shown to inhibit the formation of P. aeruginosa biofilm up to 20%. Overall these results show the potential of fucosylated oligoamides to be further developed as inhibitors of LecB binding and biofilm formation.
Keywords: LecB; fucose; glycomacromolecules; multivalent inhibitor; solid phase synthesis.
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