Synthesis of modified galacto- or fuco-clusters exploiting siderophore pathway to inhibit LecA or LecB associated virulence of Pseudomonas aeruginosa.
2020
Galacto and fuco-clusters conjugated with one to three catechol or hydroxamate motifs were synthesized to target LecA and LecB lectins of Pseudomonas aeruginosa (PA) localized in the outer membrane and in the bacterium. The resulting glycocluster pseudosiderophore conjugates were evaluated as Trojan horse to cross the outer membrane of (PA) thanks to iron transport. The data suggests that glycoclusters with catechol moieties were able to hijack the iron transport while those with hydroxamates showed strong non-specific interactions. Mono- and tri-catechol galactoclusters ( G1C and G3C ) were evaluated as inhibitors of the infection by PA in comparison with the free galactocluster ( G0 ). All of them exhibited an inhibitory effect between 46 to 75% at 100 mM with a higher potency than G0 . This result shows that LecA localized in the outer membrane of PA is involved in the infection mechanism.
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