Glycodendrimer PAMAM dendrimers

GLYCODENDRIMERS BASED ON POLY(AMIDOAMINES) (PAMAM) DENDRIMERS... 

A G4 PAMAM dendrimer conjugate80 (Fig. 16) has been synthesized, and in vivo studies have demonstrated its ability to protect against experimental infection by influenza A X-31 H3N2 virus in mice. In this case the glycodendrimer not only showed increased binding affinity due to the multivalency, but also facilitated the delivery of sialic acid, preventing enzymatic breakdown in vivo, and diminishing the cytotoxicity. 

FIGURE 16.3 Glycodendrimer-mediated protein aggregation in solution, (a) Structures of the Man-coated PAMAM dendrimers with G values referring to various dendrimer generations, (b) Transformation of uncomplexed Con A to the cross-linked state in the presence of a glycodendrimer. 

This review is devoted to the description of synthetic strategies for glycodendrimers synthesis. Dendrimers can be classified into three categories carbohydrate-coated, carbohydrate-centered and carbohydrate-based dendrimer. In this paper we will focus on the third one, in which the core unit is originated from a monosaccharide. Compare to classical Pamam, Boltorn cores, carbohydrate units add much more three dimension information, coded in the chirality in almost each carbon. Various coupling chemistry have been developed and are presented here glycosylation, amide bound formation, and click chemistry (thiol-ene reaction, epoxide - thiol reaction). 

Figure 13.10 Synthesis of mannose-/glucose-functionalized dendrimers. For dendrimer loading, x + y = 50% loading was used because optimal activity for glycodendrimers with concanavalin A was previously determined to occur at 50% functionalization. Remaining amines from the poly(amido amine) (PAMAM) substrate were capped as alcohols.

Glycodendrimers can be synthesized by both convergent and divergent strategies. Ideally, they can be simply prepared by conjugation of active carbohydrate derivatives onto preformed dendrimers (Scheme 11). Given the commercial availability of poly(amidoamine) (PAMAM, 56) and poly(propyleneimine) (Dab, 57) dendrimers, these amine-ending dendrimers are the most heavily exploited. 

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