Neuroscience Research,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 1, 2024
Despite
the
crucial
role
of
synaptic
connections
and
neural
activity
in
development
organization
cortical
circuits,
mechanisms
underlying
formation
functional
developing
human
cerebral
cortex
remain
unclear.
We
investigated
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid
receptor
(AMPAR)-mediated
transmission
using
organoids
(hCOs)
derived
from
induced
pluripotent
stem
cells.
Two-photon
Ca
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(11), P. 7515 - 7523
Published: March 6, 2024
Characterizing
the
protein
constituents
of
a
specific
organelle
and
neighbors
interest
(POI)
is
essential
for
understanding
function
state
networks
associated
with
POI.
Proximity
labeling
(PL)
has
emerged
as
promising
technology
efficient
spatial
proteomics.
Nevertheless,
most
enzymes
adopted
PL
still
have
limitations:
APEX
requires
cytotoxic
H2O2
activation
thus
poor
in
biocompatibility
vivo
application,
BioID
shows
insufficient
kinetics,
TurboID
suffers
from
high
background
biotinylation.
Here,
we
introduce
bacterial
tyrosinase
(BmTyr)
new
enzyme
suitable
H2O2-free,
fast
(≤10
min
living
cells),
low-background
tagging.
BmTyr
genetically
encodable
enables
subcellular-resolved
proteomics
cells.
We
further
designed
strategy
ligand-tethered
PL,
which
unveiled
surrounding
proteome
neurotransmitter
receptor
(Grm1
Drd2)
its
resident
synapse
live
mouse
brain.
Overall,
one
that
can
improve
expand
PL-based
applications
discoveries.
Smart Molecules,
Journal Year:
2024,
Volume and Issue:
2(3)
Published: Aug. 23, 2024
Abstract
In
situ
precise
detection
of
bioactive
molecules
with
high
sensitivity
and
spatiotemporal
resolution
is
essential
for
studying
physiological
events
disease
diagnosis.
The
utilization
versatile
fluorescent
probes
in
fluorescence
imaging
offers
a
powerful
tool
vivo
biomarkers
closely
associated
pathological
conditions.
However,
the
dynamic
behavior
leading
to
rapid
clearance
small
molecule
from
regions
interest
severely
compromises
their
potential
imaging.
Notably,
self‐immobilizing
that
selectively
recognize
diseased
tissues
while
improving
retention
enrichment
enable
accurate
high‐fidelity
this
review,
we
aim
summarize
strategies
employed
recent
advances
performance
precision
using
techniques.
Lastly,
discuss
prospects
challenges
promote
further
development
application
more
delicate
probes.
Chemical Reviews,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 7, 2025
The
term
"undruggable"
refers
to
proteins
or
other
biological
targets
that
have
been
historically
challenging
target
with
conventional
drugs
therapeutic
strategies
because
of
their
structural,
functional,
dynamic
properties.
Drugging
such
undruggable
is
essential
develop
new
therapies
for
diseases
where
current
treatment
options
are
limited
nonexistent.
Thus,
investigating
methods
achieve
drugging
an
important
challenge
in
medicinal
chemistry.
Among
the
numerous
methodologies
drug
discovery,
covalent
modification
has
emerged
as
a
transformative
strategy.
attachment
diverse
functional
molecules
provides
powerful
platform
creating
highly
potent
and
chemical
tools
well
ability
provide
valuable
information
on
structures
dynamics
targets.
In
this
review,
we
summarize
recent
examples
biomolecules
development
therapeutics
overcome
discovery
challenges
highlight
how
contribute
toward
particular,
focus
use
chemistry
drugs,
identification,
screening,
artificial
modulation
post-translational
modifications,
cancer
specific
chemotherapies,
nucleic
acid-based
therapeutics.
Chemical Society Reviews,
Journal Year:
2024,
Volume and Issue:
53(19), P. 9446 - 9489
Published: Jan. 1, 2024
Proteins,
which
are
ubiquitous
in
cells
and
critical
to
almost
all
cellular
functions,
indispensable
for
life.
Fluorescence
imaging
of
proteins
is
key
understanding
their
functions
within
native
milieu,
as
it
provides
insights
into
protein
localization,
dynamics,
trafficking
living
systems.
Consequently,
the
selective
labeling
target
with
fluorophores
has
emerged
a
highly
active
research
area,
encompassing
bioorganic
chemistry,
chemical
biology,
cell
biology.
Various
methods
selectively
tissues
have
been
established
continually
being
developed
visualize
characterize
proteins.
This
review
highlights
findings
reported
since
2018,
focus
on
small
organic
biological
applications
studying
protein-associated
events.
We
also
discuss
strengths
weaknesses
each
approach
utility
Accounts of Chemical Research,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 11, 2024
ConspectusSelective
chemical
modification
of
endogenous
proteins
in
living
systems
with
synthetic
small
molecular
probes
is
a
central
challenge
biology.
Such
has
variety
applications
important
for
biological
and
pharmaceutical
research,
including
protein
visualization,
functionalization,
proteome-wide
profiling
enzyme
activity,
irreversible
inhibition
activity.
Traditional
chemistry
selective
cells
largely
relies
on
the
high
nucleophilicity
cysteine
residues
to
ensure
target-selectivity
site-specificity
modification.
More
recently,
lysine
residues,
which
are
more
abundant
surfaces,
have
attracted
attention
covalent
proteins.
However,
it
been
difficult
efficiently
modify
ε-amino
groups
side-chains,
mostly
(∼99.9%)
protonated
thus
exhibit
low
at
physiological
pH.
Our
group
revealed
that
Analytical Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 3, 2025
The
sensitivity,
selectivity,
and
accuracy
of
immobilized
protein-based
methods
are
critically
dependent
on
the
strategies
employed
for
protein
immobilization.
Compared
with
random
immobilization
approaches,
site-specific
covalent
have
emerged
as
promising
alternatives,
offering
enhanced
analytical
performance.
However,
these
typically
require
genetic
modification
target
to
incorporate
a
specific
tag
or
prior
purification
protein,
posing
significant
challenges
immobilizing
endogenous
proteins.
Herein,
we
address
limitations
by
using
5-hydroxytryptamine
transporter
(5-HTT)
model
system.
We
designed
probe
conjugating
fluvoxamine─a
ligand
5-HTT─with
either
fluorescent
reporter
aminopropyl-modified
silica
gel
through
an
alkyl
linker
containing
acyl
imidazole
moiety
reactive
group.
By
introducing
ligand-directed
(LDAI)
chemistry,
achieved
selective
labeling
5-HTT
in
live
cells
without
advance.
Labeling
experiments
confirmed
high
specificity
favorable
kinetics
LDAI
ligands
toward
5-HTT.
Chromatographic
analysis
revealed
improvements
selectivity
(5.7-50.9-fold),
resolution
(1.2-3.0-fold),
sensitivity
(1.0-12.0-fold)
analyzing
canonical
when
5-HTT,
compared
His-tagged
Halo-tagged
recombinant
This
approach,
substituting
fluvoxamine
other
probe,
can
be
generalized
wide
range
proteins,
versatile
platform
advanced
techniques.
