Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Synthetic variants of mycolactone bind and activate Wiskott-Aldrich syndrome proteins.
[wiskott-aldrich syndrome]
Mycolactone
is
a
complex
macrolide
toxin
produced
by
Mycobacterium
ulcerans
,
the
causative
agent
of
skin
lesions
called
Buruli
ulcers
.
Mycolactone-mediated
activation
of
neural
(
N
)
Wiskott-
Aldrich
syndrome
proteins
(
WASP
)
induces
defects
in
cell
adhesion
underpinning
cytotoxicity
and
disease
pathogenesis
.
We
describe
the
chemical
synthesis
of
23
novel
mycolactone
analogues
that
differ
in
structure
and
modular
assembly
of
the
lactone
core
with
its
northern
and
southern
polyketide
side
chains
.
The
lactone
core
linked
to
southern
chain
was
the
minimal
structure
binding
N-WASP
and
hematopoietic
homolog
WASP
,
where
the
number
and
configuration
of
hydroxyl
groups
on
the
acyl
side
chain
impacted
the
degree
of
binding
.
A
fluorescent
derivative
of
this
compound
showed
time-dependent
accumulation
in
target
cells
.
Furthermore
,
a
simplified
version
of
mycolactone
mimicked
the
natural
toxin
for
activation
of
WASP
in
vitro
and
induced
comparable
alterations
of
epithelial
cell
adhesion
.
Therefore
,
it
constitutes
a
structural
and
functional
surrogate
of
mycolactone
for
WASP
/
N-WASP-dependent
effects
.
