Chemistry Reference
In-Depth Information
The calcium ion system may be most helpful for understanding lectins that have
extended binding sites or that have proximal receptor sites and may suggest that
enthalpy and entropy each dominate in specific binding situations. A helpful discus-
sion of enthalpy and entropy as they relate to multivalency is found in a recent review
article by Handl et al. (2004). A recent review by Whitesides' group provides a dis-
cussion of the energetics of multivalency as well as examples of glycosystems that
have been used successfully for the study of multivalent interactions of biological
relevance (Krishnamurthy et al. 2006).
We functionalized G4, G5, and G6-PAMAM dendrimers with mixtures of
mannose and glucose in varying ratios (Fig. 13.10) and evaluated the relative
affinities of these compounds for ConA using the hemagglutination assay. We
observed a linear trend in the binding constants for all generations that was dependent
on the relative degree of functionalization of the dendrimer with mannose and
glucose. As the ratio of mannose to glucose increased, the relative activity in the
hemagglutination assay (on a per sugar basis) increased linearly (Fig. 13.11).
Methyl mannose is bound to ConA with a fourfold higher affinity than methyl
glucose; multivalency amplified this trend. For generations 4 and 5, the difference
between mannose and glucose-functionalized dendrimers was just under 16, and gen-
eration 6 had an only slightly lower value near 11 (Wolfenden and Cloninger 2005).
Sixteen is the difference that is predicted using Eq. (1), which was proposed by
Mammen et al. (1998).
K
poly
N
¼
(K
mono
)
aN
(13
:
1)
where N is the number of receptor-ligand interactions, K
mono
is the monovalent
association constant, K
poly
is the multivalent binding constant, and ais the coopera-
tivity constant. For the man/glc dendrimers shown in Figure 13.10, no cooperative
binding is likely and a¼ 1.
Figure 13.11 Hemagglutination inhibition assay results for the interaction of mannose-/
glucose-functionalized dendrimers with concanvalin A. (
†
) G(3), (B) G(4), (V) G(5), and
(O) G(6).
