Perylenediimide-based glycoclusters as high affinity ligands of bacterial lectins: synthesis, binding studies and anti-adhesive properties

Abstract

The synthesis of eight perylenediimide-based glycoclusters was readily performed from hexa- and tetra-propargylated cores through azide-alkyne "click" conjugation. Variations in the carbohydrate epitope (Glc, Gal, Man, Fuc) and the linker arm provided molecular diversity. Interactions with LecA and LecB, two proteins involved in the adhesion of Pseudomonas aeruginosa to host tissues, were evaluated by microcalorimetry (ITC). In both cases high affinities were obtained with K values in the nanomolar range. Further evaluation of their anti-adhesive properties using cultured epithelial cells demonstrated their potent anti-adhesive activities against Pseudomonas aeruginosa with only 30-40% residual adhesion observed. The fluorescence properties of the PDI core were then investigated by confocal microscopy on cell-bacteria cultures. However, the red fluorescence signal of the PDI-based glycocluster was too weak to provide significant data. The present study provides another type of anti-adhesive glycocluster against bacterial infection with a large aromatic PDI core.

Development of Pseudomonas aeruginosa Lectin LecA Inhibitor by using Bivalent Galactosides Supported on Polyproline Peptide Scaffolds

“…[16] Another approach to enhancei nhibitor interaction to LecA is through multivalent binding. Because LecA is at etrameric lectin andt he two closest binding sites are separated by about 26 , [17] various artificial scaffolds including dendrimers, [11,[18][19][20][21][22][23][24] clusters, [12][13][14][25][26][27][28][29][30][31][32] and linear rigid spacers [33][34][35][36] have been exploited to present galactoside ligands to theb inding sites to enhancei nhibition activity. [37] In other cases, the artificial scaffoldsa re furtherf unctionalized to generate extra interactions with LecA for stronger binding.…”

Tetraphenylethylene-based glycoclusters with aggregation-induced emission (AIE) properties as high-affinity ligands of bacterial lectins

“…PDI-based glycoclusters could provide weak fluorescence in cell adhesion assays, but yet not strong enough to allow potential application as imaging agents. 13 In comparison, TPE-based glycoclusters could not be applied in the same context since their fluorescence in the blue range was overlapping with the intrinsic fluorescence of PAO1.…”

“…Glycoclusters have been designed with a large series of aromatic cores 1 among which several inherently fluorescent scaffolds. [2][3][4][5][6][7][8][9][10][11][12] We have recently applied perylenediimide (PDI) to the antiadhesive strategy 13 against Pseudomonas aeruginosa (PA) and evaluated successfully PDI-based glyco-dots in the context of cancer cells detection. 14 As a continuation of these investigations, we report here the tetraphenylethylene(TPE)-based glycoclusters as multivalent lectin ligands and also for their antiadhesive evaluation against PA.…”

Supramolecular Assembly of TPE‐Based Glycoclusters with Dicyanomethylene‐4H‐pyran (DM) Fluorescent Probes Improve Their Properties for Peroxynitrite Sensing and Cell Imaging

“…[11] Glycoclusters are watersoluble and typically display high affinity for cell surface receptors andh ave been thusu sed for targeted cell imaging and drug delivery. [12] Recently,t hrough the self-assembly between perylenediimide (PDI)-based galactoclusters and aD Md ye, we have developed aw ater-soluble supramolecular "glyco-dot" system fort he targeted fluorescencei maging of liver cancer cells that over-express galactose receptors. [13] However,i nt hat study DM was only used as an imaging agent rather than a chemicalprobe for sensingi ntracellular signaling molecules.…”

“…However, the fluorescence properties of DM‐based probes were generally influenced by the aggregation‐caused quenching (ACQ) effect from the low water‐solubility in PBS buffer thus restricting the sensitivity and further biological applications [11] . Glycoclusters are water‐soluble and typically display high affinity for cell surface receptors and have been thus used for targeted cell imaging and drug delivery [12] . Recently, through the self‐assembly between perylenediimide (PDI)‐based galactoclusters and a DM dye, we have developed a water‐soluble supramolecular “glyco‐dot” system for the targeted fluorescence imaging of liver cancer cells that over‐express galactose receptors [13] .…”