Untitled

Abstract

Clusters of di-, tri-, and tetra-antennary alpha-D-mannopyranosides were synthesized in good yields based on the coupling of amine-bearing mono- or trisaccharide [Man alpha(1 --> 6)[Man alpha(1 --> 3)]Man] haptens to poly-isocyanate or -isothiocyanate tethering cores. The relative binding properties of the resulting multivalent ligands were determined by turbidimetric and solid phase enzyme-linked lectin assays (ELLA) using plant lectins (phytohemagglutinins) Concanavalin A (Con A) and Pisum sativum (pea lectin) having four and two carbohydrate binding sites, respectively. Rapid and efficient cross-linking between tetravalent Con A and mannopyranosylated clusters were measured by a microtiter plate version of turbidimetric analyses. In inhibition of binding of the lectins to yeast mannan, the best tetravalent monosaccharide (30) and trisaccharide (31) inhibitors were shown to be 140 and 1155 times more potent inhibitors than monomeric methyl alpha-D-mannopyranoside against pea lectin and Con A, respectively. Compounds 30 and 31 were thus 35- and 289-fold more potent than the reference monosaccharide based on their hapten contents. As a general observation, the ligands bearing the Man alpha(1 --> 6)[Man alpha(1 --> 3)]Man trimannoside structures were found to be more potent inhibitors for Con A than the ligands having single mannoside residues, whereas pea lectin could not discriminate between the two types of ligands.

Synthetic Multivalent Ligands as Probes of Signal Transduction

“…These issues are relevant because the architecture of a multivalent ligand --its shape, orientation of REs, flexibility, size, valency --can influence its biological activity and its mechanism of action. [99][100][101] For instance, in systems that are activated by receptor clustering, the most potent ligands may be those with many, closelyspaced REs. Such defined ligand features may be attained using chemical synthesis.…”

Probing multivalent carbohydrate–lectin interactions by an enzyme-linked lectin assay employing covalently immobilized carbohydrates

“…4.3.5. Protocol for the ELLA employing covalently modified microtiter plates (34). This assay was carried out as described above for microtiter plates with noncovalently immobilized porcine stomach mucin except that 100 lL per well of each ABTS solution and H 2 SO 4 were used.…”

“…[30][31][32][33][34] Microtiter plates are coated with a reference ligand (often a (neo)glycoprotein or polysaccharide) and IC 50 values for inhibition of the binding of an enzyme-labeled lectin to the immobilized reference ligand (the matrix) by the soluble ligands to be tested are determined. The advantage of ELLA compared to solid-phase binding assays such as surface plasmon resonance (SPR) 35 is that both, lectin and ligand are in solution.…”

Mannosylated G(0) Dendrimers with Nanomolar Affinities to Escherichia coli FimH

“…[14] Several studies [15][16][17][18][19] have described examples of glycodendriPentaerythritol and bis-pentaerythritol scaffolds were used for the preparation of first generation glycodendrimers bearing aryl a-dmannopyranoside residues assembled using single-step Sonogashira and click chemistry. The carbohydrate precursors were built with either para-iodophenyl, propargyl, or 2-azidoethyl aglycones whereas the pentaerythritol moieties were built with terminal azide or propargyl groups, respectively.…”