Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

Abstract

SummaryThis paper describes the synthesis of three closely related families of mannopyranoside-containing dendrimers for the purpose of studying subtle structural parameters involved in the measurements of multivalent carbohydrate–protein binding interactions. Toward this goal, two trimers 5 and 9, three 9-mers 12, 17, 21, and one 27-mer 23, varying by the number of atoms separating the anomeric and the core carbons, were synthesized using azide–alkyne cycloaddition (CuAAc). Compound 23 was prepared by an efficient convergent strategy. The sugar precursors consisted of either a 2-azidoethyl (3) or a prop-2-ynyl α-D-mannopyranoside (7) derivative. The solvodynamic diameters of 9-mer 12, 17, and 21 were determined by pulsed-field-gradient-stimulated echo (PFG-STE) NMR experiments and were found to be 3.0, 2.5, and 3.4 nm, respectively.

Effect of Dendrimer Generation and Aglyconic Linkers on the Binding Properties of Mannosylated Dendrimers Prepared by a Combined Convergent and Onion Peel Approach

“…2-Bromoethyl 2,3,4,6-tetra-O-acetyl-α- d -manno-pyranoside ( 18 ) [ 27 , 51 ]. Compound 17 (5.37 g, 13.8 mmol) and 2-bromoethanol (0.98 mL, 13.8 mmol) were dissolved in DCM (50 mL).…”

“…2-Azidoethyl 2,3,4,6-tetra-O-acetyl-α- d -manno-pyranoside ( 19 ) [ 27 , 51 ]. Compound 18 (1.40 g, 3.0 mmol) and sodium azide (1.00 g, 15.4 mmol) were dissolved in anhydrous DMF (30 mL) and stirred at 80 °C for 5 h. The reaction mixture was filtered and concentrated to dryness under reduced pressure and further processed as given in general procedure ( II ) to afford compound 19 (0.75 g, 60%) as white powder.…”

“…Furthermore, multivalent carbohydrate-protein interactions have unequivocally displayed several advantages over monomeric ones, a process commonly used by nature to control a wide variety of cellular processes [ 17 , 18 , 19 ]. Hence, several glycodendrimers have been designed to address the issue of low affinity carbohydrate-protein interactions [ 5 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Mannosylated glycodendrimers were found to be excellent ligands against the leguminous lectin from Canavalia ensiformis (Concanavalin A) and to be excellent ligands toward the fimbriated E. coli K12 with nanomolar affinities [ 21 , 26 , 28 , 29 ].…”

A fast track strategy toward highly functionalized dendrimers with different structural layers: an “onion peel approach”

“…The dendri-mer diameters in solution were calculated with the help of dynamic light scattering (DLS) and diffusion NMR spectroscopy experiments (Table 1). Diffusion NMR experiments were carried out in methanol at 25 °C to measure diffusion coefficients D. 35 The corresponding solvodynamic diameters (D s = 2 × R s ) were calculated using the Stokes-Einstein equation and the viscosity of pure CD 3 OD (Table 1). The sizes of the dendrimers were also obtained using DLS technique in methanol.…”