Synthesis of glycopolymers for the study of lectin-carbohydrate interactions

Saccharides act important roles in many biological processes as recognition molecules, signalling molecules and adhesion molecules. However, due to the complexity and diversity of oligosaccharides the direct synthetic approaches cannot fully meet the demands for all of the pure and well-defined oligosaccharides being studied in glycobiology. The efficient synthesis of glycomimetics, glycopolymers, offers an attractive route to solve this problem. Thus, the synthesis and application of glycopolymers of various architectures has been extensively investigated. Meanwhile, In order to explore the mechanism of the lectin-carbohydrate interactions and to get a better understanding of the structure-function relationship of oligosaccharides, the assays employed in studies of lectin-carbohydrate interactions become much more sophisticated and accurate with fast development of various analytical approaches. In this work, well-defined glycopolymers were prepared by the combination of CCTP and CuAAC click reactions. Alkyne-containing polymer scaffolds were synthesised by CCTP, followed by post-modification of the clickable polymer scaffolds with sugar azides. Moreover, a library of well-defined synthetic glycopolymers featuring the same macromolecular properties (architecture, polydispersity, valency, polarity, etc.) with difference only in the densities of different sugars (mannose, galactose and glucose) were employed to investigate the influence of different pendant epitopes on the interactions with a model lectin Con A by the traditional methods. Additionally, two powerful modem detection techniques QCM-D and SPR were also exploited to investigate the interactions of the lectin Con A, PNA, or DC-SIGN with a series of different glycopolymers. The diversities of binding properties contributed by different clustering parameters can make it possible to define the structures of the multivalent ligands and densities of binding epitopes for specific functions in the lectin-carbohydrate interactions. These conclusions can be employed as the springboard to develop new glycopolymeric drugs and therapeutic agents and to assess the mechanisms by which they work

A detailed study on understanding glycopolymer library and Con A interactions

Synthetic glycopolymers are important natural oligosaccharides mimics for many biological applications. To develop glycopolymeric drugs and therapeutic agents, factors that control the receptor-ligand interaction need to be investigated. A library of well-defined glycopolymers has been prepared by the combination of copper mediated living radical polymerization and CuAAC click reaction via post-functionalization of alkyne-containing precursor polymers with different sugar azides. Employing Concanavalin A as the model receptor, we explored the influence of the nature and densities of different sugars residues (mannose, galactose, and glucose) on the stoichiometry of the cluster, the rate of the cluster formation, the inhibitory potency of the glycopolymers, and the stability of the turbidity through quantitative precipitation assays, turbidimetry assays, inhibitory potency assays, and reversal aggregation assays. The diversities of binding properties contributed by different clustering parameters will make it possible to define the structures of the multivalent ligands and densities of binding epitopes tailor-made for specific functions in the lectin-ligand interaction. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2588–259

Synthesis of glycopolymers for the study of lectin-carbohydrate interactions

Saccharides act important roles in many biological processes as recognition molecules, signalling molecules and adhesion molecules. However, due to the complexity and diversity of oligosaccharides the direct synthetic approaches cannot fully meet the demands for all of the pure and well-defined oligosaccharides being studied in glycobiology. The efficient synthesis of glycomimetics, glycopolymers, offers an attractive route to solve this problem. Thus, the synthesis and application of glycopolymers of various architectures has been extensively investigated. Meanwhile, In order to explore the mechanism of the lectin-carbohydrate interactions and to get a better understanding of the structure-function relationship of oligosaccharides, the assays employed in studies of lectin-carbohydrate interactions become much more sophisticated and accurate with fast development of various analytical approaches. In this work, well-defined glycopolymers were prepared by the combination of CCTP and CuAAC click reactions. Alkyne-containing polymer scaffolds were synthesised by CCTP, followed by post-modification of the clickable polymer scaffolds with sugar azides. Moreover, a library of well-defined synthetic glycopolymers featuring the same macromolecular properties (architecture, polydispersity, valency, polarity, etc.) with difference only in the densities of different sugars (mannose, galactose and glucose) were employed to investigate the influence of different pendant epitopes on the interactions with a model lectin Con A by the traditional methods. Additionally, two powerful modern detection techniques QCM-D and SPR were also exploited to investigate the interactions of the lectin Con A, PNA, or DC-SIGN with a series of different glycopolymers. The diversities of binding properties contributed by different clustering parameters can make it possible to define the structures of the multivalent ligands and densities of binding epitopes for specific functions in the lectin-carbohydrate interactions. These conclusions can be employed as the springboard to develop new glycopolymeric drugs and therapeutic agents and to assess the mechanisms by which they work

Research progress in preparation and effect of surface coating on SiC fibers

SiC fiber is one of the common reinforcements for ceramic matrix composite (CMC) due to its superior characteristics such as low density, high tensile strength, excellent high temperature resistance and oxidation resistance. The preparation of coating on the surface of SiC fiber can not only improve the mechanical properties, high temperature resistance, oxidation resistance and electromagnetic functional properties of the fiber itself, but also effectively improve the bonding properties of the interface between the fiber and the matrix to promote the fracture toughness and mechanical properties of the composite. The preparation methods of surface coatings on SiC fiber were firstly reviewed in this paper by elaborating on the basic processes and related research progress of etching, deposition, chemical vapor infiltration, and precursor derived methods, and the advantages and disadvantages of different preparation methods were compared. Then the effects of coatings on SiC fibers and their reinforced composite materials were reviewed. Finally, the development trend of surface coating on SiC fibers was briefly summarized. The combination of experimental research and computational simulation can be used to simulate the real service environment of SiC fibers coatings, and the performance of fibers under extreme service conditions can be improved by preparing thermal barrier composite coatings

Investigation of glycopolymer–lectin interactions using QCM-d : comparison of surface binding with inhibitory activity

Glycopolymers offer many opportunities for interfacing synthetic materials with biological systems. However, the nature of the interactions between glycopolymers and their biological targets, lectins, and the structural features necessary to obtain high-affinity materials are not fully understood. Here, the enhancement in binding affinity of multivalent glycopolymers to their corresponding lectins is investigated by quartz-crystal microbalance with dissipation monitoring (QCM-d). This technique allows the conformation of the adsorbed polymers to be probed and the direct observation of spanning of multiple binding sites on lectin-functional surfaces. The measured affinity was compared to the anti-adhesion activity of the polymers in solution, and it is shown that increased association constants did not directly correlate with inhibitory activity

Optimised 'click' synthesis of glycopolymers with mono/di-and trisaccharides †

In this paper we investigate the optimum procedure for the post-polymerisation modification of alkynebearing polymer scaffolds with glycosyl azides. We first elaborate the one-pot synthesis of glycosyl azides, in aqueous solution, without the need for protecting groups and in multigram scale. Using these azides, the ligand tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) was shown to give the fastest kinetics for the 'click' reaction at ambient temperature, and was used to prepare homogenous oligosaccharide-modified glycopolymers. The terminal sugars of these oligosaccharides were used to introduce a-linked glucose which is typically synthetically challenging

Optimised ‘click’ synthesis of glycopolymers with mono/di- and trisaccharides

In this paper we investigate the optimum procedure for the post-polymerisation modification of alkyne-bearing polymer scaffolds with glycosyl azides. We first elaborate the one-pot synthesis of glycosyl azides, in aqueous solution, without the need for protecting groups and in multigram scale. Using these azides, the ligand tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) was shown to give the fastest kinetics for the ‘click’ reaction at ambient temperature, and was used to prepare homogenous oligosaccharide-modified glycopolymers. The terminal sugars of these oligosaccharides were used to introduce α-linked glucose which is typically synthetically challenging