Not So Bioorthogonal Chemistry
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 28, 2025
The
advent
of
bioorthogonal
chemistry
has
transformed
scientific
research,
offering
a
powerful
tool
for
selective
and
noninvasive
labeling
(bio)molecules
within
complex
biological
environments.
This
innovative
approach
facilitated
the
study
intricate
cellular
processes,
protein
dynamics,
interactions.
Nevertheless,
number
challenges
remain
to
be
addressed,
including
need
improved
reaction
kinetics,
enhanced
biocompatibility,
development
more
diverse
orthogonal
set
reactions.
While
scientists
continue
search
veritable
solutions,
remains
transformative
with
vast
potential
advancing
our
understanding
biology
medicine.
Perspective
offers
insights
into
reactions
commonly
classified
as
"bioorthogonal",
which,
however,
may
not
always
demonstrate
desired
selectivity
regarding
interactions
between
their
components
additives
or
catalysts
used
under
conditions.
Язык: Английский
Regulating the Orientation of Homobivalent Small Binders Through 3d Domain-Swapping Design
Опубликована: Янв. 1, 2025
Язык: Английский
Development of ASGR-Mediated Hepatocyte-Targeting Cytotoxic Drug Conjugates with CTSB-Cleavable Linkers Incorporating Succinimide and Succinic Acid Monoamide
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 7, 2025
The
ASGR-mediated
endocytosis
has
been
successfully
applied
to
the
hepatocyte-targeted
delivery
of
therapeutic
oligonucleotides
via
glycoconjugates.
However,
few
studies
have
explored
conjugated
small
molecules
due
challenge
cleaving
suitable
linkers
for
release
active
molecules,
which
is
especially
different
from
GalNAc-ONs
cleaved
by
deoxyribonuclease
II
in
lysosome.
In
this
study,
GalNAc-MMAE
conjugates
linked
CTSB-cleavable
were
designed
and
synthesized.
A
comprehensive
approach
revealed
that
endocytosed
ASGR
subsequently
hydrolyzed
CTSB,
releasing
MMAE.
optimized
conjugate
with
a
succinic
acid
monoamide
as
fragment
linker
demonstrated
favorable
plasma
stability,
excellent
biodistribution,
significant
antitumor
activities
vivo
weight
gain
at
effective
dose
an
orthotopic
hepatocellular
carcinoma
mouse
model.
This
research
provides
strategy
developing
anti-HCC
agents
using
GalNAc
drug
molecules.
Язык: Английский
Photocatalyzed elaboration of antibody-based bioconjugates
Beilstein Journal of Organic Chemistry,
Год журнала:
2025,
Номер
21, С. 616 - 629
Опубликована: Март 18, 2025
Antibody–drug
conjugates
(ADCs)
represent
a
promising
class
of
targeted
therapeutics,
combining
the
specificity
antibodies
with
potency
cytotoxic
drugs
to
enhance
therapeutic
efficacy
while
minimizing
off-target
effects.
The
development
new
chemical
methods
for
bioconjugation
is
essential
generate
ADCs
and
optimize
their
stability,
efficacy,
safety.
Traditional
conjugation
often
face
challenges
related
site-selectivity
heterogeneous
product
mixtures,
highlighting
need
develop
new,
innovative
strategies.
Photoredox
chemistry
emerges
as
powerful
tool
in
this
context,
enabling
precise,
mild,
selective
modifications
peptides
proteins.
By
harnessing
light
drive
transformations,
photoredox
techniques
can
facilitate
synthesis
antibody
bioconjugates.
This
perspective
will
discuss
empower
applied
functionalization.
Язык: Английский
Chemo-Click: Receptor-Controlled and Bioorthogonal Chemokine Ligation for Real-Time Imaging of Drug-Resistant Leukemic B Cells
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(44), С. 30565 - 30572
Опубликована: Окт. 23, 2024
Drug
resistance
in
B
cell
leukemia
is
characterized
by
the
coexpression
of
CXCR5
and
CXCR3
chemokine
receptors,
making
it
a
valuable
biomarker
for
patient
stratification.
Herein,
we
report
novel
platform
activatable
chemokines
to
selectively
image
drug-resistant
leukemic
cells
first
time.
The
C-terminal
derivatization
human
CXCL13
CXCL10
with
bioorthogonal
tetrazine-BODIPY
BCN
groups
retained
binding
internalization
via
their
cognate
receptors
enabled
rapid
fluorescence
labeling
CXCR5+
CXCR3+
resistant
cells─but
not
drug-susceptible
cells─via
intracellular
ligation.
This
modular
chemical
approach
offers
versatile
strategy
real-time
immunophenotyping
populations
distinct
profiles
will
accelerate
design
new
precision
medicine
tools
advance
personalized
therapies
blood
tumors.
Язык: Английский
Diverse reactivity of maleimides in polymer science and beyond
Polymer International,
Год журнала:
2024,
Номер
74(4), С. 296 - 306
Опубликована: Ноя. 5, 2024
Abstract
Maleimides
are
remarkably
versatile
functional
groups,
capable
of
participating
in
homo‐
and
copolymerizations,
Diels–Alder
(photo)cycloadditions,
Michael
additions,
other
reactions.
Their
reactivity
has
afforded
materials
ranging
from
polyimides
with
high
upper
service
temperatures
to
hydrogels
for
regenerative
medicine
applications.
Moreover,
maleimides
have
proven
be
an
enabling
chemistry
pharmaceutical
development
bioconjugation
via
straightforward
modification
cysteine
residues.
To
exert
spatiotemporal
control
over
reactions
maleimides,
multiple
approaches
been
developed
photocage
nucleophiles,
dienes,
dipoles.
Additionally,
further
substitution
the
maleimide
alkene
(e.g.
monohalo‐,
dihalo‐,
thio‐,
amino‐
methyl‐maleimides,
among
substituents)
confers
tunable
dynamicity,
as
well
responsive
mechanical
optical
properties.
In
this
mini‐review,
we
highlight
diverse
functionality
underscoring
their
notable
impact
polymer
science.
This
moiety
related
heterocycles
will
play
important
role
future
innovations
chemistry,
biomedical,
research.
©
2024
The
Author(s).
Polymer
International
published
by
John
Wiley
&
Sons
Ltd
on
behalf
Society
Chemical
Industry.
Язык: Английский