Chemistry Reference
In-Depth Information
Figure 13.8 A polylysine dendrimer.
dendrimers bearing sulfated naphthyl groups are being developed by Starpharma Ltd
to serve as antiviral topicals against herpes simplex virus (Bourne et al. 2000; see also
Starpharma Ltd Product focus: VivaGelTM). The biocompatibility and the immuno-
genicity of the dendrimers are strongly influenced by the nature of the dendrimer
end groups, indicating that dendrimers are a viable platform for many biological
applications (Duncan 2005).
Because dendrimers have orderly, monodisperse structures (compared to many
polymer systems) with reactive termini upon which carbohydrates can readily be
appended and because higher generation dendrimers that are large enough to span mul-
tiple binding sites on lectins are readily available, glycodendrimers have great utility
for the study of multivalent protein-carbohydrate interactions (Roy 2003). In one par-
ticularly elegant early example of glycodendrimer research, Zanini and Roy (1996,
1998b) synthesized sialic acid functionalized PAMAM dendrimers and showed that
the G(3)-dendrimer was 210-fold (6.7 fold per sialoside) more active than monomeric
sialoside in inhibition binding assays with Limax flavus and human a1-acid glyco-
protein. In studies with ConA, we compared the activity of mannose-functionalized
PAMAM dendrimers of different generations and with different degrees of mannose
in the hemagglutination inhibition assay. We demonstrated that G(4)- through G(6)-
PAMAMs with mannose functionalization of half of their termini (and hydroxyl
