Journal of the American Chemical Society,
Год журнала:
2022,
Номер
144(51), С. 23633 - 23641
Опубликована: Дек. 16, 2022
Sialylation,
the
addition
of
sialic
acid
to
glycans,
is
a
crucial
post-translational
modification
proteins,
contributing
neurodevelopment,
oncogenesis,
and
immune
response.
In
cancer,
sialylation
dramatically
upregulated.
Yet,
functional
biochemical
consequences
remain
mysterious.
Here,
we
establish
μMap
proximity
labeling
platform
that
utilizes
metabolically
inserted
azidosialic
introduce
iridium-based
photocatalysts
on
sialylated
cell–surface
glycoproteins
as
means
profile
local
microenvironments
across
proteome.
comparative
experiments
between
primary
cervical
cells
cancerous
cell
line
(HeLa),
identify
key
differences
in
both
global
sialome
proximal
including
solute
carrier
proteins
regulate
metabolite
ion
transport.
particular,
show
interactions
receptors
trafficking
ethanolamine
zinc
are
sialylation-dependent
impact
intracellular
levels.
These
results
method
for
interrogating
proteoglycan
function
support
role
regulating
transporters.
Current Opinion in Structural Biology,
Год журнала:
2022,
Номер
75, С. 102395 - 102395
Опубликована: Май 30, 2022
The
surface
of
all
living
cells
is
decorated
with
carbohydrate
molecules.
Hundreds
functional
proteins
bind
to
these
glycosylated
ligands;
such
binding
events
subsequently
modulate
many
aspects
protein
and
cell
function.
Identifying
ligands
for
glycan-binding
(GBPs)
a
defining
challenge
glycoscience
research.
Here,
we
review
recent
advances
that
are
allowing
protein-carbohydrate
interactions
be
dissected
an
unprecedented
level
precision.
We
specifically
highlight
how
cell-based
glycan
arrays
glyco-genomic
profiling
being
used
define
the
structural
determinants
glycan-protein
in
cells.
Going
forward,
methods
create
exciting
new
opportunities
study
glycans
physiology
disease.
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Март 6, 2024
Abstract
Immune
checkpoint
blockade
has
yet
to
produce
robust
anti-cancer
responses
for
prostate
cancer.
Sialyltransferases
have
been
shown
across
several
solid
tumours,
including
breast,
melanoma,
colorectal
and
promote
immune
suppression
by
synthesising
sialoglycans,
which
act
as
ligands
Siglec
receptors.
We
report
that
ST3
beta-galactoside
alpha-2,3-sialyltransferase
1
(ST3Gal1)
levels
negatively
correlate
with
androgen
signalling
in
tumours.
demonstrate
ST3Gal1
plays
an
important
role
modulating
tumour
evasion
through
the
synthesises
of
sialoglycans
capacity
engage
Siglec-7
Siglec-9
immunoreceptors
preventing
clearance
cancer
cells.
Here,
we
provide
evidence
expression
Siglec-7/9
their
respective
These
interactions
can
be
modulated
enzalutamide
may
maintain
treated
conclude
activity
is
critical
anti-tumour
immunity
rationale
use
glyco-immune
targeting
therapies
advanced
Journal of Biological Chemistry,
Год журнала:
2024,
Номер
300(3), С. 105675 - 105675
Опубликована: Янв. 24, 2024
The
O-glycoprotein
Mucin-2
(MUC2)
forms
the
protective
colon
mucus
layer.
While
animal
models
have
demonstrated
importance
of
Muc2,
few
studies
explored
human
MUC2
in
similar
depth.
Recent
revealed
that
secreted
is
bound
to
feces.
We
hypothesized
fecal
(HF-MUC2)
was
accessible
for
purification
and
downstream
structural
functional
characterization.
tested
this
via
histologic
quantitative
imaging
on
sections;
extraction
from
feces
proteomic
O-glycomic
characterization;
growth
metabolic
assays
vitro.
Quantitative
solid
sections
showed
a
continuous
layer
varying
thickness
along
with
barrier
functions
intact.
Lectin
profiling
HF-MUC2
several
lectins
but
weak
absent
Ulex
europaeus
1
(α1,2
fucose-binding)
Sambucus
nigra
agglutinin
(α2,6
sialic
acid-binding),
did
not
obvious
b1/b2
layers.
separated
by
electrophoresis
high
molecular
weight
glycoprotein
bands
(∼1-2
MDa).
Proteomics
Western
analysis
confirmed
enrichment
potential
MUC2-associated
proteins
extracts.
O-glycomics
diverse
fucosylation,
moderate
sialylation,
little
sulfation
vs.
porcine
colonic
murine
Muc2.
O-glycans
were
supported
Bacteroides
thetaiotaomicron
(B.
theta)
short-chain
fatty
acid
(SCFA)
production
could
be
similarly
analyzed
inflammatory
bowel
disease
stools,
which
displayed
an
altered
glycomic
profile
differential
SCFA
B.
theta
healthy
samples.
These
describe
new
non-invasive
platform
characterization
health
disease.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(43), С. 29469 - 29480
Опубликована: Окт. 17, 2024
Widely
distributed
in
nature,
sulfated
glycan
epitopes
play
important
roles
diverse
pathophysiological
processes.
However,
due
to
their
structural
complexity,
the
preparation
of
with
structurally
defined
sulfation
patterns
is
challenging,
which
significantly
hampers
detailed
elucidation
biological
functions
at
molecular
level.
Here,
we
introduce
a
strategy
for
site-specific
chemical
epitopes,
leveraging
enzymatic
sialylation
and
desialylation
processes
precisely
control
regio-specificity
disaccharide
or
trisaccharide
backbones.
Using
this
method,
library
covering
most
common
sialylated
was
prepared
high
yield
efficiency.
By
screening
microarray
library,
systematically
probed
binding
specificity
human
Siglecs
(sialic
acid-binding
immunoglobulin-type
lectins),
many
function
as
glyco-immune
checkpoints
suppress
immune
system
activation.
Our
investigation
revealed
that
serve
determinants
Siglec
affinity
specificity.
Thus,
these
findings
offer
new
insights
development
research
tools
potential
therapeutic
agents
targeting
by
modulating
signaling
pathway.
Journal of the American Chemical Society,
Год журнала:
2022,
Номер
144(51), С. 23633 - 23641
Опубликована: Дек. 16, 2022
Sialylation,
the
addition
of
sialic
acid
to
glycans,
is
a
crucial
post-translational
modification
proteins,
contributing
neurodevelopment,
oncogenesis,
and
immune
response.
In
cancer,
sialylation
dramatically
upregulated.
Yet,
functional
biochemical
consequences
remain
mysterious.
Here,
we
establish
μMap
proximity
labeling
platform
that
utilizes
metabolically
inserted
azidosialic
introduce
iridium-based
photocatalysts
on
sialylated
cell–surface
glycoproteins
as
means
profile
local
microenvironments
across
proteome.
comparative
experiments
between
primary
cervical
cells
cancerous
cell
line
(HeLa),
identify
key
differences
in
both
global
sialome
proximal
including
solute
carrier
proteins
regulate
metabolite
ion
transport.
particular,
show
interactions
receptors
trafficking
ethanolamine
zinc
are
sialylation-dependent
impact
intracellular
levels.
These
results
method
for
interrogating
proteoglycan
function
support
role
regulating
transporters.
