Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 11, 2024
We
develop
a
latent
biocompatible
cleavage
reaction
involving
the
hitherto
unexplored
interaction
between
hydroxylamines
and
cyclopropenones.
Our
study
addresses
regioselectivity
challenges
commonly
observed
in
asymmetric
cyclopropenone
transformations,
substantiated
by
variations
substrate,
Density
Functional
Theory
calculations,
Chemical Communications,
Journal Year:
2024,
Volume and Issue:
60(51), P. 6532 - 6535
Published: Jan. 1, 2024
Polysubstituted
acrylamides
are
ubiquitous
in
bioactive
molecules
and
natural
products.
However,
synthetic
methods
for
the
assembly
of
these
important
motifs
remain
underdeveloped.
Herein,
we
report
expedient
synthesis
structurally
diverse
synthetically
challenging
polysubstituted
from
readily
available
aromatic
amines,
cyclopropenones
(CpOs),
aryl
halides
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 24, 2024
Abstract
RNA
sequences
encode
secondary
and
tertiary
structures
that
impact
protein
production
other
cellular
processes.
Misfolded
RNAs
can
also
potentiate
disease,
but
the
complete
picture
is
lacking.
To
establish
more
comprehensive
accurate
structure-function
relationships,
new
methods
are
needed
to
interrogate
trap
native
conformations
in
environments.
Existing
tools
primarily
rely
on
electrophiles
constitutively
“on”
or
triggered
by
UV
light,
often
resulting
high
background
reactivity.
We
developed
an
alternative,
chemically
approach
crosslink
using
bioorthogonal
cyclopropenones
(CpOs).
These
reagents
selectively
react
with
phosphines
provide
ketenes—electrophiles
neighboring
nucleophiles
forge
covalent
crosslinks.
As
proof-of-concept,
we
synthesized
a
panel
of
CpOs
appended
them
thiazole
orange
(TO-1).
The
TO-1
conjugates
bound
model
aptamer
(Mango)
nanomolar
affinity,
confirmed
fluorescence
turn-on.
After
phosphine
administration,
crosslinks
were
formed
between
CpO
probes
RNA.
degree
crosslinking
was
both
time
dose-dependent.
further
applied
biologically
relevant
conditions.
Collectively,
this
work
expands
toolkit
for
studying
its
conformations.
Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 29, 2024
Abstract
Immunoassay
methods,
notably
enzyme‐linked
immunosorbent
assays
(ELISAs),
renowned
for
their
signal
amplification
capabilities,
are
extensively
employed
in
scientific
research
and
clinical
diagnostics.
However,
the
instability
of
enzymes
sensitivity
to
cellular
environments
present
significant
challenges
broad
application
ELISA
living
cells.
In
this
work,
we
a
bioorthogonal
(poly)catalysis‐linked
assay
(BCLISA)
designed
detection
cell
membrane
antigens,
which
involves
coupling
catalysts
based
on
small
molecules
or
polymers
antibodies.
After
screening,
opted
copper(I)‐catalyzed
azide‐alkyne
cycloaddition
(CuAAC)
as
core
reaction
system.
The
polymer‐based
exhibit
enhanced
reactivity
at
same
molecular
concentration
due
multiple
catalytic
sites.
Polytriazoles
formed
during
CuAAC
have
ability
chelate
Cu(I),
thereby
promoting
faster
catalysis.
By
harnessing
autocatalytic
feature,
successfully
increased
potential
BCLISA.
Ultimately,
autocatalysis‐integrated
BCLISA
technique
was
antigen
imaging
both
vitro
membranes.
This
approach
offers
new
method
low‐abundance
antigens
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 29, 2024
Abstract
Immunoassay
methods,
notably
enzyme‐linked
immunosorbent
assays
(ELISAs),
renowned
for
their
signal
amplification
capabilities,
are
extensively
employed
in
scientific
research
and
clinical
diagnostics.
However,
the
instability
of
enzymes
sensitivity
to
cellular
environments
present
significant
challenges
broad
application
ELISA
living
cells.
In
this
work,
we
a
bioorthogonal
(poly)catalysis‐linked
assay
(BCLISA)
designed
detection
cell
membrane
antigens,
which
involves
coupling
catalysts
based
on
small
molecules
or
polymers
antibodies.
After
screening,
opted
copper(I)‐catalyzed
azide‐alkyne
cycloaddition
(CuAAC)
as
core
reaction
system.
The
polymer‐based
exhibit
enhanced
reactivity
at
same
molecular
concentration
due
multiple
catalytic
sites.
Polytriazoles
formed
during
CuAAC
have
ability
chelate
Cu(I),
thereby
promoting
faster
catalysis.
By
harnessing
autocatalytic
feature,
successfully
increased
potential
BCLISA.
Ultimately,
autocatalysis‐integrated
BCLISA
technique
was
antigen
imaging
both
vitro
membranes.
This
approach
offers
new
method
low‐abundance
antigens
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 11, 2024
We
develop
a
latent
biocompatible
cleavage
reaction
involving
the
hitherto
unexplored
interaction
between
hydroxylamines
and
cyclopropenones.
Our
study
addresses
regioselectivity
challenges
commonly
observed
in
asymmetric
cyclopropenone
transformations,
substantiated
by
variations
substrate,
Density
Functional
Theory
calculations,