Novel Dextran‐Supported Biological Probes Decorated with Disaccharide Entities for Investigating the Carbohydrate–Protein Interactions of Gal‐3

Abstract

The quest for novel natural‐like biomolecular probes that can be used to gain information on biological recognition events is of topical interest to several scientific areas. In particular, the recognition of carbohydrates by proteins modulates a number of important biological processes. These molecular recognition events are, however, difficult to study by the use of naturally occurring oligosaccharides and polysaccharides owing to their intrinsic structural heterogeneity and to the many technical difficulties encountered during the isolation of sufficient quantities of pure material for detailed structural and biological studies. Therefore, the construction of homogenous biomolecular probes that can mimic both the biophysical properties of polysaccharide backbones and the properties of bioactive oligosaccharide fragments are highly sought after. Herein, synthetic methodology for the construction of well‐defined bioconjugates consisting of biologically relevant disaccharide fragments grafted onto a dextran backbone is presented, and a preliminary NMR spectroscopy study of their interactions with galectin‐3 as a model lectin is conducted.

Novel NMR Avenues to Explore the Conformation and Interactions of Glycans

“…The addition of lactose also gave rise to the corresponding chemical shift perturbations that were identical to those measured on diluted Gal-3/lactose samples. 85 This observation underlines the ability of the lactose to find the proper binding site even in physiological crowded media, even though the K d would reasonably be lower due to slower diffusion processes (reduced k on ) and competition with other substrates for the Gal-3 binding site. Finally, the interaction of Gal-3 with serum glycoproteins from both HSA and BSA samples was demonstrated to occur via recognition of the nonreducing 2,3-sialyllactose motif present in those glycoproteins, as evidenced by the identical set of CSP obtained for the Gal-3 HSQC spectrum when titrated with the pure 2,3-sialyllactose trisaccharide.…”

Targeting Galectins With Glycomimetics

“…A different glucose-based scaffold to bear disaccharide epitopes has been proposed by Rahkila et al ( 2019 ), consisting of a dextran skeleton decorated with LacNAc moieties. The idea behind this architecture was to mimic natural polysaccharides (Rahkila et al, 2018 ).…”

Unraveling Sugar Binding Modes to DC-SIGN by Employing Fluorinated Carbohydrates

“…The possibility of finding different molecular structures, by variation of the stereochemistry of hydroxyl groups and the regiochemistry of the glycosidic linkages, grows geometrically as compared with other linear biopolymers. Ligand-based NMR experiments are widely used to study the interactions between carbohydrates and receptors in solution [1,2,3,4]. Among these methods that are especially powerful for screening purposes, 19 F-based approaches present a number of important advantages [5,6,7,8].…”