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Tuning glycosidase inhibition through aglycone interactions: pharmacological chaperones for Fabry disease and GM1 gangliosidosis.
[gm1 gangliosidosis]
Competitive
inhibitors
of
either
α-galactosidase
(
α-
Gal
)
or
β-galactosidase
(
β-
Gal
)
with
high
affinity
and
selectivity
have
been
accessed
by
exploiting
aglycone
interactions
with
conformationally
locked
sp
(
2
)
-
iminosugars
.
Selected
compounds
were
profiled
as
potent
pharmacological
chaperones
for
mutant
lysosomal
α-
and
β-
Gal
associated
with
Fabry
disease
and
GM
(
1
)
gangliosidosis
.
