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

Abstract

Pentaerythritol and bis-pentaerythritol scaffolds were used for the preparation of first generation glycodendrimers bearing aryl alpha-D-mannopyranoside 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. Cross-linking abilities of this series of glycodendrimers were first evaluated with the lectin from Canavalia ensiformis (Concanavalin A). Surface plasmon resonance measurements showed these two families of mannosylated clusters as the best ligands known to date toward Escherichia coli K12 FimH with subnanomolar affinities. Tetramer 4 had a K(d) of 0.45 nM. These clusters were 1000 times more potent than mannose for their capacity to inhibit the binding of E. coli to erythrocytes in vitro.

Boron Drug Delivery via Encapsulated Magnetic Nanocomposites: A New Approach for BNCT in Cancer Treatment

“…A literature method was used to immobilize propargyl groups by the reaction of propargyl bromide with the hydroxyl groups on the starch matrix covering the surface of magnetic nanoparticles [37]. Under an argon atmosphere, with vigorous magnetic stirring, 10.0 mL (108.85 mmol, great excess) of propargyl bromide was slowly added to a solution of 200.0 mg magnetic nanoparticles suspended in a mixed solvent of 30.0 mL of DMF and 5.0 mL of deionized water followed by the addition of 5.0 g of NaOH.…”

‘Click’ assembly of glycoclusters and discovery of a trehalose analogue that retards Aβ40 aggregation and inhibits Aβ40-induced neurotoxicity

“…Supplementary data associated with this article (including novel and literaturederived 18,[26][27][28][29][30]35,40,46,48,61,[64][65][66] experimental content) can be found, in the online version, at…”

“…Hexa-alkyne 2 was obtained by alkylating dipentaerythritol (1) with propargyl bromide under phase-transfer conditions similar to those used by Nouguier and McHich to alkylate pentraerythritol. 26 An alternative synthesis of 2 adapted from the method used by Touaibia et al to alkylate pentraerythritol, 27 involving reaction of dipentaerythritol (1) with propargyl bromide in DMF/KOH, was inferior (6% yield) to the phase-transfer method (33% yield). Peracetylated β-glucosyl azide 3 and peracetylated β-galactosyl azide 4 were prepared from the corresponding 1,2,3,4,6-penta-O-acetyl-β-D-glycopyranoses by treatment with with 33% HBr in AcOH to form the 2,3,4,6-tetra-O-acetyl-α-D-glycopyranosyl bromides, followed by immediate nucleophilic displacement with NaN 3 in a phase-transfer reaction according to the method of Tropper et al 28 Peracetylated β-lactosyl azide 5 was synthesized by first acetylating lactose with Ac 2 O/NaOAc and recrystallizing the crude product from hot MeOH to give 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-Dgalactopyranosyl)-β-D-glucopyranose.…”

An efficient synthesis of D-galactose-based multivalent neoglycoconjugates

“…For example, L-fucoside and D-galactose-coated glycodendrimers were effective in blocking P. aeruginosa lectin PA-IL and PA-IIL, 8 while D-mannose-coated ones were able to inhibit the binding of E. coli to epithelial cells. 9 Recently, anti-inflammatory activity was reported for D-glucose-based glycodendrimers. 10 Due to the importance of neoglycoconjugates for these biological studies, there is a constant need for straightforward methods for the synthesis and purification of these compounds.…”