Chemistry Reference
In-Depth Information
Figure 17.4
Schematic drawing of bacteria
(left) and viruses (right) adhering to the cell
surface via binding of the glycan chains of gly-
coproteins. Inhibition of attachment is accom-
plished by a multivalent glycoconjugate carrying
several copies of glycans capable of binding
bacterial and viral lectins. Multivalent presenta-
tion of the inhibitory carbohydrate is necessary
for effi cient blocking to occur.
TWIG - a carbosilane dendrimer) copies of the p
k
trisaccharide (Gal
1,4Glc),
respectively, were effective in protecting mice from the pathogenic effects of
shiga-like toxins produced by enterohemorrhagic
E. coli
[26] . A polyacrylamide
conjugate substituted with Neu5Ac
α
1,4Gal
β
1,4GlcNAc protected mice infected by
infl uenza virus. Natural peptide-based scaffolds, such as mucins, carrying multiple
substitution of
O
-glycans can be regarded as natural polymers with a multivalent
presentation of bioactive glycans [27]. Such molecules carrying the SLe
x
or Le
b
determinants were shown to be effi cient inhibitors of
H. pylori
adhesion (please
see Chapter 3.9 for synthetic route to Le
b
) [27] .
Very few clinical trials have been performed with multivalent, carbohydrate-
based inhibitors of microbial adhesion. Orally administrated silicon dioxide parti-
cles carrying covalently linked Gb3 failed to diminish the severity of disease in
children with diarrhea-associated hemolytic uremic syndrome. However, further
development of multivalent inhibitors and more clinical trials are to be expected;
innovative developments that will pave the way for tangible advances in the fi eld.
α
2,6Gal
β
17.4
Conclusions
Bacterial lectins can be found at the tip and/or along the shaft of a fi mbriae or
pili, or can be expressed directly on the bacterial surface. Some bacterial lectins
constitute subunits in bacterial toxins. Their common denominator is to facilitate
host cell attachment and to promote infection. Protein-carbohydrate interactions
