One‐Pot Multicomponent Synthesis of Glycopolymers through a Combination of Host–Guest Interaction, Thiol‐ene, and Copper‐Catalyzed Click Reaction in Water

Abstract

There is a common phenomenon that the heterogeneity of natural oligosaccharides contains various sugar units, which can be used to enhance affinity and selectivity toward a specific receptor, so the synthesis of heterogeneous glycopolymers is always an important issue in the glycopolymer field. Herein, this study conducts a one-pot method to prepare polyrotaxane-based heteroglycopolymers anchored with different sugar units and fluorescent moieties via the combination of host-guest interaction, thiol-ene, and copper-catalyzed click chemistry in water. Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography, X-ray diffraction, and Ellman's assay test are used in the paper to characterize the compounds. Quartz crystal microbalance-dissipation (QCD-D) experiments and bacterial adhesion assay are utilized to study the interactions of polyrotaxane-based heteroglycopolymers with Con A and Escherichia coli. The results reveal that polyrotaxanes (PRs) with mannose and glucose present better specificity toward Con A and E. coli than PRs with glucose due to synergistic effects.

Mannosylated Polyrotaxanes for Increasing Cellular Uptake Efficiency in Macrophages through Receptor-Mediated Endocytosis

“…To date, mannose-modified α-CD/poly(ethylene glycol) (PEG)-based PRXs or pseudo-PRXs have been synthesized using a click reaction between azidated PRXs and propargyl mannose [26,27,28,29]. Although the click reaction is highly efficient for introducing functional molecules on PRXs, it requires the introduction of azide or alkyne groups.…”

Cyclodextrin-Based Functional Glyconanomaterials

“…Pioneering work in this area was conducted by the groups of Stoddart [64], Yui [65], Sasabe [66] and Fort [67] and has already been reviewed [23]. In 2017, Gao, Chen and coworkers proposed a one-pot multicomponent synthesis of pseudopolyrotaxane-based heteroglycopolymers anchored with different sugar units and fluorescent moieties via the combination of host-guest interaction, thiol-ene and copper(I)-catalyzed click chemistry in water [68]. The interest in multivalent (nano)systems exposing more than just a single type of saccharide motif has greatly increased in the last years after the publication of a cumulative number of reports describing synergistic effects in lectin binding, a phenomenon termed heterocluster effect [69][70][71][72][73][74][75].…”

Glycopolymers Mimicking GM1 Gangliosides: Cooperativity of Galactose and Neuraminic Acid for Cholera Toxin Recognition

“…[14] Therefore, deconstructing oligosaccharides into smaller carbohydrate modules and reconstructing them as ap olymeric mimic with carbohydrate modules displayed on the polymer sidechaini sauseful approach to obtain the cluster glycoside effect and mimic the function of natural carbohydrates. [15] Although the carbohydrate module methodi sa na ttractive approach, there remain challenges. Natural carbohydrates are composed of multiple carbohydrate modules, and not all are involved in the interactions with proteins.S omem odulesa re necessary for protein interactions, and othersa re required for determining the steric conformation.…”

“…synthesized a mimic of SLe X using glycopolymers bearing galactose, fucose, and neuraminic acid moieties, which were shown to be capable of selectin recognition . Therefore, deconstructing oligosaccharides into smaller carbohydrate modules and reconstructing them as a polymeric mimic with carbohydrate modules displayed on the polymer sidechain is a useful approach to obtain the cluster glycoside effect and mimic the function of natural carbohydrates …”