Metabolites,
Год журнала:
2024,
Номер
14(12), С. 668 - 668
Опубликована: Дек. 2, 2024
Covalent
modification
of
proteins
at
specific,
predetermined
sites
is
essential
for
advancing
biological
and
biopharmaceutical
applications.
Site-selective
labeling
techniques
protein
allow
us
to
effectively
track
function,
intracellular
dynamics,
localization.
Despite
numerous
reports
on
modifying
target
with
functional
chemical
probes,
unique
organic
reactions
that
achieve
site-selective
integration
without
compromising
native
properties
remain
a
significant
challenge.
In
this
review,
we
delve
into
using
synthetic
highlighting
both
computational
methodologies
chemo-
regioselective
modifications
naturally
occurring
amino
acids,
as
well
proximity-driven
protein-selective
modifications.
We
also
underline
recent
traceless
affinity
strategies
involve
exchange/cleavage
catalyst
tethering
The
rapid
development
infrastructure
methods
has
made
the
bioconjugation
more
accessible,
enabling
precise
predictions
structural
changes
due
Hence,
discuss
bioconjugational
approaches,
including
molecular
dynamics
artificial
intelligence,
underscoring
their
potential
applications
in
enhancing
our
understanding
cellular
biology
addressing
current
challenges
field.
Chemical Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Exploiting
quantitative
and
reversible
site-selective
disulfide
modification
as
a
means
for
selective
lysine
functionalisation
on
clinically
relevant
antibody
fragments.
Chemical Reviews,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 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.
Ecotoxicology and Environmental Safety,
Год журнала:
2024,
Номер
279, С. 116495 - 116495
Опубликована: Май 30, 2024
Abrus
cantoniensis
Hance
(ACH)
is
an
ancient
Chinese
medicine
herb
known
for
its
therapeutic
effects.
This
study
investigated
the
potential
protective
effect
of
ACH
against
carbon
tetrachloride
(CCl
ACS Chemical Biology,
Год журнала:
2024,
Номер
19(7), С. 1554 - 1562
Опубликована: Июнь 26, 2024
Small
molecular
tool
compounds
play
an
essential
role
in
the
study
of
G
protein-coupled
receptors
(GPCRs).
However,
most
often
occupy
orthosteric
binding
site,
hampering
GPCRs
upon
ligand
binding.
To
overcome
this
problem,
ligand-directed
labeling
techniques
have
been
developed
that
leave
a
reporter
group
covalently
bound
to
GPCR,
while
allowing
subsequent
ligands
bind.
In
work,
we
applied
such
strategy
adenosine
A
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 19, 2024
Targeting
the
lysine
residue
of
protein
kinases
to
develop
covalent
inhibitors
is
an
emerging
hotspot.
Herein,
we
have
reported
approach
lysine-targeted
PI3Kδ
by
in
situ
interaction
upgradation
H-bonding
bonding.
Several
warhead
groups
were
introduced
and
screened
situ,
leading
bearing
aromatic
esters
with
high
bioactivity
selectivity.
Compound
A11
phenolic
ester
was
finally
optimized
show
a
long
duration
action
SU-DHL-6
cells
multiple
assays.
Docking
simulation
further
mass
spectrometry
confirmed
that
bound
covalent-bonding
interactions
Lys779.
Furthermore,
exhibited
potently
antitumor
efficacy
without
obvious
toxicity
Pfeiffer
xenograft
mouse
models.
This
study
identified
be
much
more
effective
agent
vitro
vivo
as
inhibitor,
it
also
provided
practical
for
development
inhibitors.
Accounts of Chemical Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 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
