Biomimetic Tweezers for N‐Glycans: Selective Recognition of the Core GlcNAc₂ Disaccharide of the Sialylglycopeptide SGP

Abstract

In recent years, glycomics have shown how pervasive the role of carbohydrates in biological systems is and how chemical tools are essential to investigate glycan function and modulate carbohydrate-mediated processes. Biomimetic receptors for carbohydrates can carry out this task but, although significant affinities and selectivities toward simple saccharides have been achieved, targeting complex glycoconjugates remains a goal yet unattained. In this work we report the unprecedented recognition of a complex biantennary sialylglycopeptide (SGP) by a tweezers-shaped biomimetic receptor, which selectively binds to the core GlcNAc 2 disaccharide of the N-glycan with an affinity of 170 μM. Because of the simple structure and the remarkable binding ability, this biomimetic receptor can represent a versatile tool for glycoscience, opening the way to useful applications.

Towards Biomimetic Recognition of Glycans by Synthetic Receptors

“…More recently the same tweezer‐shaped architecture proved to be also effective in targeting of the GlcNAc 2 disaccharide within the core structure of a complex N‐glycan [109] . Indeed, the tetraphosphonate analogue 31 (Figure 9), prepared to circumvent the self‐association phenomenon of the progenitor 30 , demonstrated the capability to intercept and strongly recognize the GlcNAc 2 disaccharide at the stem of sialoglycopeptide SGP with the same affinity observed for the disaccharide ($${{BC}_{50}^{0}}$$ =1.7×10 −4 M).…”

A Macrocyclic Tweezers‐Shaped Receptor for the Biomimetic Recognition of the Gal(α1‐3)Gal Disaccharide of the α‐Gal Antigen

“…Despite the interesting results obtained with monosaccharides, 1 shows only moderate binding abilities toward disaccharides, mainly because of the size of the macrocyclic cavity. [26] Conversely, a homologous member of the family (2, Figure 1), [27,28] which shows a tweezerslike shape and a single diaminocarbazole hydrogen-bonding unit in an open-chain architecture, does not bind to monosaccharides, but exhibits peculiar recognition properties toward disaccharides, in particular toward the N,N'-diacetylchitobiose (βGlcNAc 2 ), even when this is present in the core structure of Nglycans.…”

Dynamic Approach to Synthetic Lectin for Glucose with Boosted Binding Affinity through C−H Hydrogen Bonds

“…Carbohydrate is a critical component in various biological processes, [1,2] such as energy storage, intercellular communication, and immune response. Synthetic receptors [3][4][5][6][7][8][9][10][11] that bind carbohydrates have the potential to facilitate the investigation of their biological functions and the creation of new therapeutic and diagnostic agents, such as anti-infective agents, synthetic antibodies, and carbohydrate sensors. The development of synthetic receptors [12][13][14] for glucose, in particular, holds significant implications for managing blood glucose levels in diabetes.…”