Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from Burkholderia cenocepacia

The opportunistic Gram-negative bacterium Burkholderia cenocepacia causes lethal infections in cysticfibrosis patients. Multivalent mannoside derivatives were prepared as potential inhibitors of lectin BC2LA,one of the virulence factors deployed by B. cenocepacia in the infection process. An (a1/2)-thiolinkedmannobioside mimic bearing an azide functionalized aglycon was conjugated to differentmultivalent scaffolds such as propargylated calix[4]arenes, methyl gallate and pentaerythritol by azidealkyne1,3-dipolar cycloaddition. The interaction between the glycoclusters and the mannose bindingBC2L-A lectin from B. cenocepacia was examined by isothermal microcalorimetry, surface plasmonresonance, inhibition of yeast agglutination and analytical ultracentrifugation.