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OBn
OBn
BnO
P
O
O
O
O
O
O
HO
HN
HO
OH
HO
2
C
OH
OH
O
OH
O
O
BnO
O
O
O
O
O
O
HN
O
O
HO
O
BnO
O
HO
NH
O
+
Ph
OH
O
OH
O
O
BnO
H
N
3
53
(GM3NPhAc)
CuI, DIPEA
THF/ MeOH
24h
52
OBn
OBn
BnO
P
O
O
O
O
O
O
O
HN
BnO
O
O
O
O
O
O
BnO
NH
O
O
O
BnO
NH
O
N
N
N
O
HO
Ph
HO
OH
OH
O
NH
O
O
O
O
O
HO
HO
OH
CO
2
H
OH
OH
OH
54
SCHEME 13.10
Coupling of alkyne-containing MPLA
52
with the azide-derived
GM3NPhAc
53
, through click reaction, to afford the neoglycoconjugate
54
.
a variety of linker length was synthesized to mimic the GDP moiety and interact in
the hydrophobic pocket adjacent to the binding site of the acceptor molecule using
a click chemistry strategy (Scheme 13.11) [40]. The inhibition of the human
-1,3-
fucosyltransferase VI (Fuc-T VI) was evaluated, and showed that molecule
55
had
the highest activity, with
K
i (comp) 62 nM, being a competitive inhibitor against
GDP-fucose and the first nanomolar and most potent inhibitor of Fuc-Ts already
described. On the other hand, a noncompetitive mechanism was observed when the
enzymatic assays were performed against the acceptor molecule,
N
-acetyllactosamine
(LacNAc), with a
K
i (noncomp) of 221
±
8 nM [40].
13.4.2 Mannosyltransferases
Mannosyltransferase(s) may play a role for
Leishmania
amastigotes survival in
macrophages, since it is involved in the biosynthesis of
-1,2-mannan and/or
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