Chemistry Reference
In-Depth Information
mind, research on synthetic multivalent macromolecules has intensifi ed, giving
rise to several original glycoconjugate structures that constitute high-affi nity mul-
tivalent ligands that target surface receptors (that is enzymes, lectins, toxins,
viruses and bacteria). These multivalent glycoconjugates have shown great poten-
tial as effective inhibitors of cell-pathogen interactions (Figure 4.3) (please see
Chapter 17 for further details on bacterial/viral lectins). Notable examples include
multivalent sialic acid and mannoside molecules that bind to the hemagglutinin
receptor on the infl uenza virus surface or the FimH at the tip of pilliated
Esche-
richia coli (E. coli)
, where the multivalent enhancement factor ranges from 10 to
10
6
, depending on the degree of valency and type of scaffolds utilized [4]. Here,
again, the chemist's creativity has provided the impetus for access to highly elegant
and effective architectures [5] .
Figure 4.3
Blocking bacterial/viral infections by competitive binding to host tissues with glycodendrimers.
4.2
How to Prepare Multivalent Carbohydrates?
A thorough understanding of multivalent carbohydrate- protein interactions
suffers from the natural carbohydrate complexities that are also the result of
incomplete biosynthesis or subtle attachment of other functionalities at specifi c
positions along the oligosaccharide sequences (sulfate, phosphate, acetate, and so
on; for substituted sugars such as mannose- 6 - phosphate on the HNK - 1 epitope,
please see Chapter 1, especially Figure 1.7). In order to study, characterize, under-
stand and manipulate these critical interactions, striking advances in isolation,
purifi cation, structural analyses and partial or selective degradation processes have
been achieved, albeit with limited amounts of the resulting glycoconjugates (for
further details, please see Chapter 5). Hence, chemical or chemoenzymatic syn-
