Rim-differentiation vs. mixture of constitutional isomers: A binding study between pillar[5]arene-based glycoclusters and lectins from pathogenic bacteria

Macrocycle-based glycoclusters, on account of their promising anti-adhesive properties against bacteria, are potential therapeutic alternatives to classic antibiotics through the much less explored strategy. In this study, a series constitutionally-pure pentavalent glycoclusters was prepared by conjugating assorted azido-carbohydrates onto penta-propargyl rim-differentiated pillar[5]arene (RD-P[5]) scaffold Cu(I)-catalyzed azide–alkyne cycloaddition “click” reactions. Their binding towards therapeutically relevant bacterial lectins, such as LecA and LecB from Pseudomonas aeruginosa concanavalin A (ConA), were evaluated subsequently isothermal titration calorimetric studies. Most these isomer-free RD-P[5] except fucosylated ones, display good affinities lectins. Nonetheless, dissociation constants observed similar those displayed an analogous glycocluster consisting four P[5] constitutional isomers, in which component merely accounts for 7% mixture. Our results revealed that high purity is not essential achieving effective multivalent interactions between P[5]-based presumably result conformationally labile nature scaffold. This information provides valuable design principles low-cost facile syntheses glycosylated P[5]s biomedical applications.