Chemistry Reference
In-Depth Information
+
Na
-
O
3
SO
O
O
N
O
N
HO
O
C
O
N
HO
N
OH
OSO
3
-
Na
+
O
O
O
N
O
HO
N
3
O
C
O
N
N
HO
OH
O
N
OSO
3
-
Na
+
O
O
O
N
O
HO
O
C
O
N
N
HO
OH
N
110
N
N
N
N
3
HO
HO
HO
HO
HO
O
HO
HO
HO
O
O
O
O
O
O
O
O
O
DMF-water
O
O
3
3
3
3
3
3
3
3
3
3
CuSO
4
, Cu(0)
NaAsc
9
9
9
9
9
9
9
9
9
9
S
S
S
S
S
S
S
S
S
S
111
112
SCHEME 6.21
Click
glycocoating
of
self-assembled
monolayers
(SAMs)
for
high-
throughput characterization of carbohydrate-lectin interactions.
6.7 CLICK MULTIVALENT GLYCOMIMETICS
The carbohydrate-binding sites in lectins are very often superficially located, so that
the bound ligand remains largely in contact with bulk solvent. On the other hand, lectin
molecules tend to form oligomers and those oligomers can be expressed as clusters.
All these are factors that contribute to the multivalent effect by facilitating sliding of
multivalent conjugates over carbohydrate-binding sites, favoring chelate-type com-
plexes, and promoting cross-linking and aggregation. The low binding affinities for
monovalent ligands also favor fast on-off binding kinetics after increasing the local
concentration through multivalent presentation, limiting the entropic penalty of the
association. In principle, one could expect that some of those processes could also
be at play in the interaction of carbohydrates with other receptor partners. Recently,
the possible existence of a multivalent effect in the interaction of carbohydrates
with carbohydrate-processing enzymes has attracted the attention of several groups.
Should it operate, then one could hypothesize that a conceptually new type of enzyme
inhibitors could be designed by displaying glycomimetic structures, capable of com-
petitively competing with the substrate for the catalytic site, in multiple copies. For
obvious reasons, click chemistry has been privileged to test this notion.
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