European Journal of Chemistry,
Год журнала:
2024,
Номер
15(4), С. 355 - 365
Опубликована: Дек. 31, 2024
Bioorthogonal
chemistry
has
emerged
as
a
pivotal
field
in
molecular
science,
offering
transformative
tools
for
applications
drug
discovery,
imaging,
and
biology.
This
review
provides
comprehensive
analysis
of
recent
advancements
bioorthogonal
chemistry,
emphasizing
key
innovations,
practical
applications,
future
research
directions.
We
explore
state-of-the-art
reactions,
including
Staudinger
ligation,
strain-promoted
azide-alkyne
cycloaddition
(SPAAC),
tetrazine
detailing
their
mechanisms,
advantages,
limitations.
The
highlights
significant
innovations
such
novel
fluorogenic
probes,
improved
catalysts,
enhanced
reaction
conditions
that
have
expanded
the
utility
efficiency
these
reactions.
Practical
are
examined,
showing
how
advances
revolutionized
fields
like
live-cell
targeted
delivery,
labeling.
Looking
to
future,
we
discuss
emerging
trends
potential
avenues,
integration
with
other
advanced
technologies
development
new
methodologies.
detailed
overview
current
state
outlines
its
potential,
serving
valuable
resource
researchers
practitioners
field.
Chemical Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Tetrazine-based
fluorogenic
labels
are
widely
utilized
in
medical
and
biological
studies,
exhibiting
substantial
fluorescence
enhancement
(FE)
following
tetrazine
degradation
through
bio-orthogonal
reactions.
However,
the
underlying
mechanisms
driving
this
response
remain
only
partially
resolved,
particularly
regarding
diminished
FE
efficiency
deep-red
near-infrared
(NIR)
regions.
This
knowledge
gap
has
impeded
efforts
to
optimize
these
for
extended
emission
wavelengths
improved
ratios.
review
offers
a
photophysical
perspective,
discussing
quenching
pathways
(i.e.,
energy
flows
charge
separation)
that
regulate
properties
exhibited
various
types
of
labels.
Moreover,
work
examines
emerging
role
intramolecular
rotations
certain
tetrazine-based
structures
integration
additional
quencher
units.
The
proposed
alternative
channel
potential
surpass
traditional
wavelength
constraints
while
achieving
FE.
By
examining
mechanisms,
aims
advance
understanding
tetrazine-functionalized
provide
guiding
principles
their
future
design
practical
applications.
Chemical Communications,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
This
feature
article
provides
a
detailed
overview
of
the
synthesis,
properties
and
applications
sydnonimines,
fascinating
compounds
from
mesoionic
familly.
Chemistry - A European Journal,
Год журнала:
2024,
Номер
30(48)
Опубликована: Авг. 9, 2024
Abstract
Bioinspired
molecular
engineering
strategies
have
emerged
as
powerful
tools
that
significantly
enhance
the
development
of
novel
therapeutics,
improving
efficacy,
specificity,
and
safety
in
disease
treatment.
Recent
advancements
focused
on
identifying
utilizing
disease‐associated
biomarkers
to
optimize
drug
activity
address
challenges
inherent
traditional
such
frequent
administrations,
poor
patient
adherence,
increased
risk
adverse
effects.
In
this
review,
we
provide
a
comprehensive
overview
latest
developments
bioinspired
artificial
systems
(BAS)
use
tailor
therapeutic
responses
drugs
presence
disease‐specific
biomarkers.
We
examine
transition
from
open‐loop
systems,
which
rely
external
cues,
closed‐loop
feedback
capable
autonomous
self‐regulation
response
detail
various
BAS
modalities
designed
achieve
biomarker‐driven
therapy,
including
activatable
prodrug
molecules,
smart
delivery
platforms,
cells,
synthetic
receptor‐based
cell
therapies,
elucidating
their
operational
principles
practical
vivo
applications.
Finally,
discuss
current
future
perspectives
advancement
BAS‐enabled
technology
envision
ongoing
toward
more
programmable
customizable
BAS‐based
therapeutics
will
precision
medicine.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 23, 2024
Abstract
Proteolysis
targeting
chimeras
(PROTACs)
hold
immense
promise
for
targeted
protein
degradation;
however,
challenges
such
as
off‐target
effects,
poor
drug‐likeness
properties,
and
the
“hook
effect”
remain.
This
study
introduces
Nano‐Click‐formed
PROTACs
(Nano‐CLIPTACs)
precise
tumor
degradation
in
vivo.
Traditional
with
high
molecular
weight
were
first
divided
into
two
smaller
druglike
precursors
capable
of
self‐assembling
to
form
functional
through
a
bioorthogonal
reaction.
Then,
optimal
CLIPTACs
(
W4
Z2
)
encapsulated
individually
cyclic
RGDfC‐peptide‐modified
liposomes
prepare
Nano‐CLIPTACs,
enabling
tumor‐targeted
delivery
subsequent
situ
self‐assembly
WZ42
within
cells.
The
abilities
Nano‐CLIPTACs
vitro
vivo
further
verified
using
key
oncology
target,
anaplastic
lymphoma
kinase
(ALK),
validating
safety,
efficacy
“anti‐hook
this
strategy.
Overall,
represent
critical
step
towards
clinical
translation
technology
anti‐cancer
therapies.
Angewandte Chemie,
Год журнала:
2024,
Номер
136(47)
Опубликована: Авг. 8, 2024
Abstract
Der
Einsatz
hochwirksamer,
aber
zugleich
toxischer
Antibiotika
wie
Colistin
ist
aufgrund
der
Zunahme
antimikrobieller
Resistenzen
unvermeidlich
geworden.
Wir
berichten
hier,
geschütztes
chemisch
am
Ort
Infektion
kontrolliert
mithilfe
von
click‐to‐release‐Reaktionen
freigesetzt
werden
kann,
um
seine
systemische
Toxizität
zu
verringern.
Kinetische
Experimente
mit
neun
Tetrazinen
und
drei
Dienophilen
zeigten
eine
besonders
schnelle
Wirkstoff‐Freisetzung
über
Diels–Alder‐Reaktion
inversem
Elektronenbedarf
zwischen
einem
trans‐Cycloocten
(TCO)
dem
aminfunktionalisierten
Tetrazin
Tz7
.
Die
antibiotische
Aktivität
gegen
Escherichia
coli
wurde
durch
TCO‐Einheiten
maskiert,
die
Reaktion
d
‐Ubi−Tz
,
Tetrazin,
das
an
Bakterien
bindenden
Peptid
D‐Ubi
29–41
funktionalisiert
ist,
wiederhergestellt.
Während
neutral
geladenes
TCO
gegenüber
humanen
proximalen
Tubulus‐Nierenzelllinie
HK‐2
nicht
verbesserte,
verringerte
Asparaginsäure
modifiziertes
Gesamtladung
des
Peptids
den
Eintritt
in
Nierenzellen,
wodurch
drastisch
verringert
wurde.
Das
Analogon
Col−(TCO‐Asp)
1
zeigte
bei
Mäusen
günstige
pharmakokinetische
Eigenschaften
vivo
Infektionsmodell
lokal
Lunge
aktiviert,
während
es
ohne
chemischen
Auslöser
inaktiv
blieb.
Diese
Studie
liefert
erste
Beispiel
für
ein
systemisch
wirkendes
Zweikomponenten‐Antibiotikum
verbesserter
Arzneimittelverträglichkeit.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(47)
Опубликована: Авг. 8, 2024
Abstract
The
use
of
highly
potent
but
very
toxic
antibiotics
such
as
colistin
has
become
inevitable
due
to
the
rise
antimicrobial
resistance.
We
aimed
for
a
chemically‐triggered,
controlled
release
at
infection
site
lower
its
systemic
toxicity
by
harnessing
power
click‐to‐release
reactions.
Kinetic
experiments
with
nine
tetrazines
and
three
dienophiles
demonstrated
fast
via
an
inverse‐electron‐demand
Diels–Alder
reaction
between
trans
‐cyclooctene
(TCO)
amine‐functionalised
tetrazine
Tz7
.
antibiotic
activity
against
Escherichia
coli
was
masked
TCO
units,
restored
upon
d
‐Ubi−Tz
,
functionalised
bacterial
binding
peptide
‐Ubi
29–41
While
standard
did
not
improve
human
proximal
tubular
kidney
HK‐2
cells,
installation
aspartic
acid‐modified
masking
group
reduced
overall
charge
entry
thereby
dramatically
lowering
toxicity.
analog
Col−(TCO‐Asp)
1
had
favourable
pharmacokinetic
properties
in
mice
successfully
activated
locally
lung
vivo
model,
whereas
it
remained
inactive
non‐harmful
without
chemical
trigger.
This
study
constitutes
first
example
systemically
acting
two‐component
improved
drug
tolerability.
Angewandte Chemie,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 23, 2024
Abstract
The
development
of
innovative
strategies
enabling
chemical
reactions
in
living
systems
is
great
interest
for
exploring
and
manipulating
biological
processes.
Herein,
we
present
a
pioneering
approach
based
on
both
bioorthogonal
confined
chemistry
intracellular
drug
synthesis.
Exploiting
click‐to‐release
reaction,
engineered
nanoparticles
capable
synthesizing
drugs
within
cellular
environments
through
with
cyclooctynes.
Proof
concept
experiments
showed
that
this
new
could
be
successfully
applied
to
the
synthesis
FDA‐approved
Sorafenib
cancer
cells.
integration
not
only
offers
exciting
prospects
advancing
therapeutic
but
also
opens
up
avenues
non‐natural
systems.
This
represents
fundamental
extension
biorthogonal
holds
promise
developments
applications.
