Chemistry Reference
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Figure 13.14 Fucose-/galactose-functionalized antibacterial dendrimers.
demonstrated that the multifunctional dendrimers were selectively cytotoxic for KB
cells that overexpress folic acid (Majoros et al. 2006). Again, although carbohydrates
were not used in this research, the highly multifunctional nature of the dendrimers
demonstrates the importance of heterofunctionalized multivalent dendrimers in
cancer research.
Dendrimers bearing more than one carbohydrate have been used not only with
plant lectins (see previous example from Wolfenden and Cloninger 2005, 2006)
but also with bacterial lectins. Deguise et al. (2007) incorporated galactose and
fucose residues onto dendrimers (Fig. 13.14). The different sugars were on different
halves of the dendrimers, with “click” chemistry as the method of carbohydrate
attachment. Dendrimers bearing both carbohydrates were capable of binding to
PA-IL and PA-IIL, two lectins from Pseudomonas aeruginosa. PA-IL exhibits speci-
ficity for
D
-galactose whereas PA-IIL displays preferential binding to
L
-fucose, and
control experiments indicated that the glycodendrimer/lectin binding occurred
through selective lectin-carbohydrate interactions. This report demonstrates that
dendrimers bearing more than one carbohydrate can bind to orthogonal targets and
represents an important advance for the use of glycodendrimers in multivalent
processes (Deguise et al. 2007).
13.5. COMMENTS REGARDING THE SYNTHESIS OF
HETEROMULTIVALENT CARBOHYDRATE SYSTEMS
Roy's research group (Deguise et al. 2007) synthesized dendrimers with fucoside on
half of the dendrimer and galactoside on the other half using a convergent “outside-
in” synthetic procedure. Linear polymers capable of displaying multiple carbo-
hydrates in different segments of the polymer were reported by Pontrello et al.
(2005). As demonstrated with Roy's fucose/galactose dendrimers, frameworks that
can display blocks of carbohydrates may be preferred for some applications such
as those in which binding of more than one lectin is required. In some instances,
small molecules bearing two carbohydrates (or two ligands of any kind) may be
able to attract larger multivalent systems into appropriate displays to induce desired
