Opportunities for Therapeutic Modulation of O-GlcNAc
Chemical Reviews,
Год журнала:
2024,
Номер
124(22), С. 12918 - 13019
Опубликована: Ноя. 7, 2024
O-Linked
β-N-acetylglucosamine
(O-GlcNAc)
is
an
essential,
dynamic
monosaccharide
post-translational
modification
(PTM)
found
on
serine
and
threonine
residues
of
thousands
nucleocytoplasmic
proteins.
The
installation
removal
O-GlcNAc
controlled
by
a
single
pair
enzymes,
transferase
(OGT)
O-GlcNAcase
(OGA),
respectively.
Since
its
discovery
four
decades
ago,
has
been
diverse
classes
proteins,
playing
important
functional
roles
in
many
cellular
processes.
Dysregulation
homeostasis
implicated
the
pathogenesis
disease,
including
neurodegeneration,
X-linked
intellectual
disability
(XLID),
cancer,
diabetes,
immunological
disorders.
These
foundational
studies
disease
biology
have
motivated
efforts
to
target
therapeutically,
with
multiple
clinical
candidates
under
evaluation.
In
this
review,
we
describe
characterization
biochemistry
OGT
OGA,
regulation,
development
OGA
inhibitors,
pathophysiology,
progress
modulators,
emerging
opportunities
for
targeting
O-GlcNAc.
This
comprehensive
resource
should
motivate
further
study
into
function
inspire
strategies
therapeutic
modulation
Язык: Английский
Comprehensive evaluation of S-glyco-modification in vitro based on the potential impacts to Michael addition
Bioorganic Chemistry,
Год журнала:
2025,
Номер
161, С. 108522 - 108522
Опубликована: Апрель 30, 2025
Язык: Английский
Fast Metabolic Glycan Labeling for Click-Labeling and Imaging of Sialoglycans in Living Acute Brain Slices from Mice and Human Patients
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(31), С. 22008 - 22016
Опубликована: Июль 30, 2024
Living
acute
brain
slices
provide
a
practical
platform
for
imaging
sialylation
in
human
pathology.
However,
the
limited
lifespan
of
has
impeded
use
metabolic
glycan
labeling
(MGL),
which
requires
long-term
incubation
clickable
unnatural
sugars
such
as
N-azidoacetylmannosamine
(ManNAz)
to
metabolically
incorporate
azides
into
sialoglycans.
Here,
we
report
fast
variant
MGL
(fMGL),
ManNAz-6-phosphate
enables
efficient
azidosugar
incorporation
within
12
h
by
bypassing
bottleneck
step
sialic
acid
biosynthesis
pathway,
followed
click-labeling
with
fluorophores
and
sialoglycans
from
mice
patients.
In
clinical
samples
ganglioglioma,
fMGL-based
reveals
specific
upregulation
astrocyte-like
but
not
neuron-like
tumor
cells.
addition,
fMGL
is
integrated
click-expansion
microscopy
high-resolution
slices.
The
strategy
should
find
broad
applications
tissue
glycans
surgical
Язык: Английский
Visualizing DNA/RNA, Proteins, and Small Molecule Metabolites within Live Cells
Small,
Год журнала:
2024,
Номер
20(46)
Опубликована: Авг. 3, 2024
Live
cell
imaging
is
essential
for
obtaining
spatial
and
temporal
insights
into
dynamic
molecular
events
within
heterogeneous
individual
cells,
in
situ
intracellular
networks,
vivo
organisms.
Molecular
tracking
live
cells
also
a
critical
general
requirement
studying
physiological
processes
biology,
cancer,
developmental
neuroscience.
Alongside
this
context,
review
provides
comprehensive
overview
of
recent
research
progress
live-cell
RNAs,
DNAs,
proteins,
small-molecule
metabolites,
as
well
their
applications
diagnosis,
immunodiagnosis,
biochemical
diagnosis.
A
series
advanced
techniques
have
been
introduced
summarized,
including
high-precision
imaging,
high-resolution
low-abundance
multidimensional
multipath
rapid
computationally
driven
methods,
all
which
offer
valuable
disease
prevention,
treatment.
This
article
addresses
the
current
challenges,
potential
solutions,
future
development
prospects
field.
Язык: Английский
Investigation of relationships between metabolic chemical reporter structures and S-glyco-modification effects
Biao Dou,
Menghe Wang,
Wenfeng Guo
и другие.
Bioorganic Chemistry,
Год журнала:
2024,
Номер
151, С. 107717 - 107717
Опубликована: Авг. 12, 2024
Язык: Английский
Demystifying Multipronged Approaches of Wheat Germ Agglutinin-Mediated Drug Delivery, Targeting, and Imaging: An Explicative Review
Journal of Drug Delivery Science and Technology,
Год журнала:
2024,
Номер
unknown, С. 106307 - 106307
Опубликована: Окт. 1, 2024
Язык: Английский
Xylosyltransferase Bump-and-hole Engineering to Chemically Manipulate Proteoglycans in Mammalian Cells
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 20, 2023
Abstract
Mammalian
cells
orchestrate
signalling
through
interaction
events
on
their
surfaces.
Proteoglycans
are
an
intricate
part
of
these
interactions,
carrying
large
glycosaminoglycan
polysaccharides
that
recruit
molecules.
Despite
importance
in
development,
cancer
and
neurobiology,
a
relatively
small
number
proteoglycans
have
been
identified.
In
addition
to
the
complexity
glycan
extension,
biosynthetic
redundancy
first
protein
glycosylation
step
by
two
xylosyltransferase
isoenzymes
XT1
XT2
complicates
annotation
proteoglycans.
Here,
we
develop
chemical
genetic
strategy
manipulates
attachment
site
cellular
By
employing
tactic
termed
bump-
and-hole
engineering,
engineer
specifically
transfer
chemically
modified
xylose
analogue
target
proteins.
The
modification
contains
bioorthogonal
tag,
allowing
ability
visualise
profile
proteins
both
transferases
mammalian
cells.
versatility
our
approach
allows
pinpointing
sites
tandem
mass
spectrometry,
exploiting
handle
manufacture
with
defined
GAG
chains
for
applications.
Engineered
XT
enzymes
permit
view
into
proteoglycan
biology
is
orthogonal
conventional
techniques
biochemistry.
Язык: Английский