Angewandte Chemie,
Год журнала:
2023,
Номер
135(30)
Опубликована: Апрель 20, 2023
Abstract
This
study
describes
the
development
of
a
new
type
amine‐reactive
superhydrophobic
(RSH)
film
that
is
facilely
coated
on
various
substrates
using
single‐step
process,
while
versatility
this
RSH
offers
reliable
solution
for
efficient
formation
complex
and
robust
interlayer
electrical
connectivity
(IEC)
in
3D
electronic
systems.
The
excellent
spatial
controllability
surface
amine
modification
enables
generation
vertical
circuits
situ,
providing
distinct
way
to
connect
located
different
layers.
Moreover,
inherent
superhydrophobicity
porosity
exhibit
required
anti‐fouling
breathability
properties,
making
RSH‐based
IEC
well‐suited
applications
where
exposure
environmental
gas
liquid
contaminants
likely.
approach
provides
another
avenue
towards
flexible
integrated
electronics,
opening
up
possibilities
advancement
field.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(36)
Опубликована: Июль 13, 2023
Glycoengineering
has
provided
powerful
tools
to
construct
site-specific
antibody
conjugates.
However,
only
small-molecule
payloads
can
be
directly
transferred
native
or
engineered
antibodies
using
existing
glycoengineering
strategies.
Herein,
we
demonstrate
that
reducing
the
complexity
of
crystallizable
fragment
(Fc)
glycans
could
dramatically
boost
chemoenzymatic
modification
immunoglobulin
G
(IgG)
via
an
fucosyltransferase.
In
this
platform,
with
Fc
a
simple
N-acetyllactosamine
(LacNAc)
disaccharide
are
successfully
conjugated
biomacromolecules,
such
as
oligonucleotides
and
nanobodies,
in
single
step
within
hours.
Accordingly,
synthesized
antibody-conjugate-based
anti-human
epidermal
growth
factor
receptor
2
(HER2)/
cluster
differentiation
3
(CD3)
bispecific
used
it
selectively
destroy
patient-derived
cancer
organoids
by
reactivating
endogenous
T
lymphocyte
cells
(T
cells)
inside
organoid.
Our
results
highlight
platform
is
general
approach
antibody-biomacromolecule
conjugates
translational
values.
Angewandte Chemie,
Год журнала:
2023,
Номер
135(36)
Опубликована: Июль 13, 2023
Abstract
Glycoengineering
has
provided
powerful
tools
to
construct
site‐specific
antibody
conjugates.
However,
only
small‐molecule
payloads
can
be
directly
transferred
native
or
engineered
antibodies
using
existing
glycoengineering
strategies.
Herein,
we
demonstrate
that
reducing
the
complexity
of
crystallizable
fragment
(Fc)
glycans
could
dramatically
boost
chemoenzymatic
modification
immunoglobulin
G
(IgG)
via
an
fucosyltransferase.
In
this
platform,
with
Fc
a
simple
N‐acetyllactosamine
(LacNAc)
disaccharide
are
successfully
conjugated
biomacromolecules,
such
as
oligonucleotides
and
nanobodies,
in
single
step
within
hours.
Accordingly,
synthesized
antibody‐conjugate‐based
anti‐human
epidermal
growth
factor
receptor
2
(HER2)/
cluster
differentiation
3
(CD3)
bispecific
used
it
selectively
destroy
patient‐derived
cancer
organoids
by
reactivating
endogenous
T
lymphocyte
cells
(T
cells)
inside
organoid.
Our
results
highlight
platform
is
general
approach
antibody‐biomacromolecule
conjugates
translational
values.
ACS Macro Letters,
Год журнала:
2024,
Номер
13(11), С. 1551 - 1557
Опубликована: Окт. 31, 2024
Organometallic
oxidative
addition
complexes
(OACs)
have
recently
emerged
as
a
powerful
class
of
reagents
for
the
rapid
and
chemoselective
modification
biomolecules.
Notably,
steric
electronic
properties
ligand
aryl
group
can
be
modified
to
tune
kinetic
profile
reaction
permit
regioselective
S-arylation.
Using
developed
dicyclohexylphosphine-based
bidentate
P,N-ligated
Au(III)
OACs,
we
computationally
experimentally
examined
effects
sterically
bulky
electron
deficient
substrates
achieve
selective
With
this
mechanistic
insight,
based
on
4-iodoanisole
3,5-dimethyl-4-iodoanisole
were
incorporated
end
groups
generate
heterotelechelic
bis-Au(III)
poly(ethylene
glycol)
(PEG).
This
reagent
performed
S-arylation
with
model
biomolecule,
designed
ankyrin
repeat
protein
(DARPin),
form
protein–polymer
OAC
in
situ.
mediated
second
biologically
relevant
thiolated
small
molecules
(metal
chelator,
saccharide,
fluorophore)
macromolecules
(polymer
therapeutic
peptide).
It
is
envisioned
that
approach
could
utilized
construction
biomacromolecular
heteroconjugates
S-aryl
linkages.
Nucleic Acids Research,
Год журнала:
2024,
Номер
52(19), С. 11587 - 11601
Опубликована: Сен. 24, 2024
Abstract
Epigenetic
aberration
is
one
of
the
major
driving
factors
in
human
cancer,
often
leading
to
acquired
resistance
chemotherapies.
Various
small
molecule
epigenetic
modulators
have
been
reported.
Nonetheless,
outcomes
from
animal
models
and
clinical
trials
underscored
substantial
setbacks
attributed
pronounced
on-
off-target
toxicities.
To
address
these
challenges,
CRISPR/dCas9
technology
emerging
as
a
potent
tool
for
precise
modulation
mechanism.
However,
this
involves
co-expressing
exogenous
modulator
proteins,
which
presents
technical
challenges
preparation
delivery
with
potential
undesirable
side
effects.
Recently,
our
research
demonstrated
that
Cas9
tagged
Phe-Cys-Pro-Phe
(FCPF)-peptide
motif
can
be
specifically
targeted
by
perfluorobiphenyl
(PFB)
derivatives.
Here,
we
integrated
FCPF-tag
into
dCas9
established
chemically
inducible
platform
epigenome
editing,
called
Chem-CRISPR/dCas9FCPF.
We
designed
series
chemical
inhibitor-PFB
conjugates
targeting
various
proteins.
Focusing
on
JQ1,
panBET
inhibitor,
demonstrate
c-MYC-sgRNA-guided
JQ1-PFB
inhibits
BRD4
close
proximity
c-MYC
promoter/enhancer,
thereby
effectively
repressing
intricate
transcription
networks
orchestrated
compared
JQ1
alone.
In
conclusion,
Chem-CRISPR/dCas9FCPF
significantly
increased
target
specificity
inhibitors,
offering
viable
alternative
conventional
fusion
protein
systems
editing.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 29, 2024
The
recent
emergence
of
organometallic
chemistry
for
modification
biomolecular
nanostructures
has
begun
to
rewrite
the
long-standing
assumption
among
practitioners
that
small-molecule
organometallics
are
fundamentally
incompatible
with
biological
systems.
This
Perspective
sets
out
clarify
some
existing
misconceptions
by
focusing
on
growing
toolbox
modification.
Specifically,
we
highlight
key
transformations
in
constructing
complex
biologically
relevant
systems
nanomolecular
scale,
and
synthesis
hybrid
nanomaterials
composed
classical
nanomaterial
components
combined
species.
As
research
progresses,
many
challenges
associated
applying
this
context
rapidly
being
reassessed.
Looking
future,
utility
will
likely
make
them
more
ubiquitous
construction
nanostructures.
Chemical Communications,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 9, 2024
The
π-clamp-mediated
conjugation
method,
which
enables
site-specific
modification
of
cysteine
residues,
is
a
promising
strategy
for
developing
well-defined
radiolabelled
biomolecules
positron
emission
tomography
(PET)
imaging.
We
have
applied
this
method
to
site-specifically
attach
the
macrocyclic
chelators
"NODA"
and
"NODAGA"
somatostatin
receptor
2-targeted
peptide,
octreotate.
resulting
novel
NODA-octreotate
NODAGA-octreotate
compounds
can
be
with
either
[
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Сен. 5, 2022
Glycoengineering
has
been
demonstrated
to
be
a
powerful
tool
construct
site-specific
antibody
conjugates.
However,
with
most
glycoengineering
strategies,
several
hours
days
are
needed
complete
the
reaction,
and
payloads
limited
small
molecules.
Herein,
we
show
that
reducing
complexity
of
Fc
glycan
could
dramatically
boost
enzymatic
IgG
molecules
achieve
unexpectedly
high
efficiency
payload
capacity.
Notably,
antibodies
modified
were
successfully
conjugated
biomacromolecules,
e.g
.,
oligonucleotides
nanobodies,
in
one
step
by
an
engineered
fucosyltransferase.
Moreover,
conversion
this
chemoenzymatic
engineering
finished
minutes,
or
up
hours,
affording
homogeneous
products.
The
trisaccharide
linker
these
conjugates
exhibits
excellent
hydrophilicity
stability
reduced
ADCC
activity.
Using
platform,
synthesized
antibody-conjugate-based
HER2/CD3
bispecific
applied
it
selectively
destroy
patient-derived
cancer
organoids
reactivating
endogenous
T
cells
inside
organoid.
These
results
suggest
format
translational
value.
Angewandte Chemie,
Год журнала:
2023,
Номер
135(30)
Опубликована: Апрель 20, 2023
Abstract
This
study
describes
the
development
of
a
new
type
amine‐reactive
superhydrophobic
(RSH)
film
that
is
facilely
coated
on
various
substrates
using
single‐step
process,
while
versatility
this
RSH
offers
reliable
solution
for
efficient
formation
complex
and
robust
interlayer
electrical
connectivity
(IEC)
in
3D
electronic
systems.
The
excellent
spatial
controllability
surface
amine
modification
enables
generation
vertical
circuits
situ,
providing
distinct
way
to
connect
located
different
layers.
Moreover,
inherent
superhydrophobicity
porosity
exhibit
required
anti‐fouling
breathability
properties,
making
RSH‐based
IEC
well‐suited
applications
where
exposure
environmental
gas
liquid
contaminants
likely.
approach
provides
another
avenue
towards
flexible
integrated
electronics,
opening
up
possibilities
advancement
field.
