Chemistry Reference
In-Depth Information
OH
HO
OH
OH
OCMP
CO
2
-
O
OH
CO
2
-
OH
O
HO
OH
OCMP
CO
2
-
HO
OH
CTP
PPi
OH
HO
HO
OH
HO
O
OH
O
NH
O
O
N
HN
N
3
O
CMP-sialic acid
synthetase
HN
HO
N
3
HO
HO
N
N
O
HO
CuAAC
OH
O
O
144
145
146
OH
HO
O
O
HO
O
OH
aldolase
α
-2,6-sialyltransferase
CO
2
-
CMP
O
N
3
OH
HN
HO
OH
CO
2
-
O
HO
OH
OH
HO
HO
HO
OH
O
O
NH
O
N
O
O
O
HO
HO
HO
N
N
O
143
OH
OH
147
OH
OCMP
CO
2
-
HO
OH
O
CTP = Cytidinetriphosphate
CMP = Cytidine monophosphate
HN
N
3
HO
O
α
-2,6-sialyltransferase
145
CMP
CO
2
-
OH
OH
OH
CO
2
-
O
HO
OH
HO
HO
HO
O
O
O
O
NH
O
OH
N
O
HN
N
3
HO
O
HO
HO
HO
O
N
OH
O
N
148
Cu, DIPEA
CH
3
CN-H
2
O
(conc. 1mM)
O
O
N
OH
N
N
O
OH
OH
NH
HO
OH
HO
O
HO
O
-
O
2
C
CO
2
-
O
OH
HN
O
OH
HO
HO
HO
HO
O
N
N
N
HO
O
O
149
SCHEME 5.31
Chemoenzymatic approach for the synthesis of macrocyclic oligosaccharide
analogs containing sialic acid units.
bacterial infections [1c-f, 3, 4]. The generally low affinity of monovalent ligands
for lectins can be overcome by using polyfunctional scaffolds displaying structurally
well-defined saccharide units. The affinity enhancements observed by using this strat-
egy can be very impressive [48, 49]. A remarkable example is the decavalent ligand
designed by Bundle and coworkers (STARFISH
R
), which inhibited Shiga-like toxins
in enzyme-linked immunosorbent assays (ELISA) with a 10
6
-fold enhancement over
the monomeric species [50].
Depending both on the nature of the receptor and on the valency and geometry of
the ligand, this gain in stability, the so-called multivalent or cluster effect [51], can
be explained by the interplay of different mechanisms, including chelation binding
Search WWH ::
Custom Search