Multivalent display of carbohydrates

In addition to dendrimers (32, 37) and clusters (33-36, 38, 39), two of the main avenues of pursuit by chemists for multivalent display of carbohydrates are neoglycopolymers (8, 40-43), and dynamic self-assembled systems (44-50) such as liposomes and micelles. Pseudopolyrotaxanes (1-4) and polyrotaxanes (18, 19) incorporate the advantages of both the polymeric and dynamic approaches. 

In another example of liposome usage, a multivalent display of a C-3-modified sialoside on liposomes has been shown to inhibit influenza virus replication [124]. Hemagglutinin and sialidase are both involved in both glycoproteins, are involved in attachment and detachment of viral particles on the host cell through recognition of sialyl residues. In this case, the C-3-modified sialoside liposome seems to be such a successful inhibitor of viral replication because it successfully targets two different enz)mes that act on multivalent carbohydrate displays. 

Even pseudopolyrotaxanes and polyrotaxanes of cyclo-dextrins threaded onto linear polymer chains have been employed to display carbohydrates and achieve dynamic multivalent glycomimetics. These beads-on-a-string have been adapted for the multivalent display of lactosides in order to bind to galectin-1. The cyclodextrins are able to spin around the axes of the polymer chains as well as move back and forth along the polymer backbones. Thus, spatial mismatches between the ligand and the receptor can be eliminated by adaptable presentation of epitopes on account of the dynamic flexibiUty of the pseudopolyrotaxane architecture. ... 

Several groups have employed polyamino acid backbones as templates for the display of multiple carbohydrate residues [164,165]. For example, potent E-selectin antagonists have been generated from poly lysine [166,167] These materials are highly effective inhibitors of leukocyte rolling. Multivalent polylysine displays have also been used to inhibit Shiga-like toxin binding [168]. 

Naturally occurring carbohydrate multivalent displays are widespread in nature and include mucins, pathogen, and mammalian cell surfaces. Lectins, carbohydrate-binding proteins, often present multiple repeat carbohydrate binding domains. The interaction of multivalent presentations can result in the formation of numerous simultaneous non-co-valent bonds that proceed to afford the observed high avidity of carbohydrates (153). 

Carbohydrate-protein interactions are usually highly speeifie. As with carbohydrate-carbohydrate interactions, multivalence is essential, beeause multiple interactions between carbohydrates and proteins are necessary to aehieve strong binding or enhanced inhibition. In pursuit of synthetic targets where carbohydrates are multiply displayed over suitable scaffolds, a number of model systems have been used to study multivalent interactions between carbohydrates and proteins.GNPs have also been used in this field, and the results have been reviewed. ... 

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