Linear Glycopolymers

With the development of controlled radical polymerization techniques like nitroxide-mediated radical polymerization (NMRP), atom transfer radical polymerization (ATRP), and reversible addition fragmentation chain transfer (RAFT) polymerization (see Section 3.2), the field of linear glycopolymers has significantly flourished, especially as control of molar mass and monomer sequence has become available, even for functionalized monomers. This enables incorporation of new and more complex glycomonomers as well as allows controlled dispersity, end group functionality, and monomer sequences in block, star-shaped, and graft copolymers, and eventually 

RAFT gained special interest, firstly because this polymerization technique works very well with polar monomers and often allows polymerization of unprotected glycomonomers (Fig. 5.19). The obtained products are usually metal-free, therefore biocompatible, and polymerization in water has been long reported. 

FIGURE 5.19 Examples of glycomonomers used in RAFT polymerization reactions. 

ATRP using an azide-modified initiator, whereby this polymer was first coupled with a fluorescent dialkyne and then with the azide-modified virus. 

The preparation of block copolymers with segments that carry glyco units and exhibit an amphiphilic character is especially interesting. These well-defined structures can be used for self-assembly processes to access more complex glycostructures. 

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Figure 13.4 A schematic showing some of the frameworks that have been reported for the study of protein-carbohydrate interactions. Carbohydrates are represented as cyclohexane. (Top) Glycodendrimer, carbohydrate-functionalized nanoparticle, and star polymer. (Bottom) Linear glycopolymer, carbohydrate-functionalized protein, and carbohydrate-functionalized surface.

Fig ure 2.1 Schematic presentation of a linear glycopolymer with pendant sugar ligands in the side chain. 

Recently, a Click polymerization strategy has been utilized to produce glycopolymers in which carbohydrates are incorporated into the backbone [198, 199]. Eissa and Khosravi demonstrated the copper wire-catalyzed Click polymerization of di-alkyne-terminated PEG with di-azide-functionalized trehalose prepared by tosylation/acetylation of a,a-D-trehalose followed by azidation reaction (Scheme 12) [199]. The produced alternating linear glycopolymers with triazole linkers were fully characterized and the polymer with a PEG segment of 600 gmol showed a lower critical solution temperature (LCST) at 39°C, which is known as the fever temperature. This material constituted a new class of temperature-responsive water-soluble glycopolymers. 

For many years Wang and his group (2d) have carried out extensive research on glycopolymers (e.g., glycosylated linear polymers or hydrogels). In their review article, they described some of the characteristics of these polymers, particularly their use as anti-adhesion drugs. 

Figure 5.9 Synthesis of glycopolymer-functionalized MWCNTs (top). Representative TEM images of linear poly(MAIG)-functionalized MWCNTs at 29 (a) and 10.5 h (b), deprotected glycopolymer-functionalized MWCNTs at 29 h (c), and the macroinitiator CNT-Br-1 (d). Reprinted with permission from Gao et al ...

Synthetic glycopolymers of various architectures have been prepared in recent years using the fast development of controlled polymerization techniques and the very efficient coupling reactions in polymer analogous approaches. Both, linear and globular polymer structures that have been obtained by synthesizing dendritic, starlike, or micelle-like structures or nanogels have received much attention. 

The most important synthetic approaches toward linear and globular/ branched glycopolymers will be highlighted here. Two main approaches are addressed preformation of reactive polymers, which can be further modified by polymer analogous reaction with sugar moieties, and direct incorporation of glyco units during the polymer formation process. 

Architecture. The advent of LRP has allowed the synthesis of cationic copolymers of well-defined architectures, hence allowing a careful analysis of the structure-activity relationship of these polymers. Synthetic linear cationic glycopolymers of statistical, block and block-statistical architectures were prepared by RAFT polymerization and studied for their gene expression profiles, as a function of molecular weight, carbohydrate content as well as architecture. The copolymers of 30-40 kDa and of... 

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