Chemistry Reference
In-Depth Information
Chart 2.5 Structure of G1cNAc-based homopolymer
(8)
and amphiphilic block
copolymer (9).
Oligosaccharides on the cell surface play an important role in various biological
recognition processes, including intercellular recognition, adhesion, cell growth,
and differentiation. For recognition of cell surfaces, polymers containing sugar
units are interesting synthetic targets. For example, amphiphilic block copolymer 9
containing isobutyl vinyl ether as the hydrophobic block and N-acetyl-
D
-glucosamine
(G1cNAc) as the hydrophilic block with pendant glucose residues has been syn-
thesized and studied (Chart 2.5; Yamada et al. 1999). These polymers have been
found to assemble and disassemble in response to variations in temperature. To
study the binding between glucosamine units and wheat germ (WGA) lectins,
a natural glycoprotein that specifically recognizes G1cNAc residues was used.
Using the tryptophan emission from the WGA lectin as the probe, the interaction
between the glucosamines in the block copolymer and the protein was monitored.
Considering several water-soluble, carbohydrate-functionalized polymers have been
studied to understand polyvalent interactions, it is interesting to question the import-
ance of studying block copolymers for this purpose. This is particularly important
considering the fact that block copolymer assemblies, such as micelles, could
reduce the accessibility of some of the ligands even within the hydrophilic
block for binding to the protein. In this study, the recognition of these polymers
was compared with that of homopolymer 8 and corresponding monomers. Both
polymer types exhibited higher binding affinity compared to the monomeric
GlcNAc (6.8
10
2
M
21
). For the polymer containing 20 repeat units of GlcNAc
functionality, block copolymer 9 exhibited a binding affinity of 3.3
10
5
M
21
com-
pared to 5.9
10
4
M
21
for homopolymer 8 with the same number of repeat units. The
Hill coefficient for both of these polymers was found to be the same, 2.3. The fivefold
enhancement in binding affinity for the block copolymer could be attributed to pre-
organization. Nonetheless, it is interesting to note that the eventual encapsulation
does seem to play a role in the binding affinity, because when the degree of polymer-
ization was increased to 38, the difference in binding affinity between the homopo-
lymer and the block copolymer decreased significantly.
To understand whether the preorganization in a block copolymer assembly indeed
provides any advantages in presenting multivalent ligand copies, one could envision
the presentation of a single copy of a specific ligand at the hydrophilic chain terminus
