Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Feb. 21, 2023
Abstract
Genetic
encoding
of
noncanonical
amino
acid
(ncAA)
for
site-specific
protein
modification
has
been
widely
applied
many
biological
and
therapeutic
applications.
To
efficiently
prepare
homogeneous
multiconjugates,
we
design
two
encodable
acids
(ncAAs),
4-(6-(3-azidopropyl)-s-tetrazin-3-yl)
phenylalanine
(pTAF)
3-(6-(3-azidopropyl)-s-tetrazin-3-yl)
(mTAF),
containing
mutually
orthogonal
bioorthogonal
azide
tetrazine
reaction
handles.
Recombinant
proteins
antibody
fragments
the
TAFs
can
easily
be
functionalized
in
one-pot
reactions
with
combinations
commercially
available
fluorophores,
radioisotopes,
PEGs,
drugs
a
plug-and-play
manner
to
afford
dual
conjugates
assess
tumor
diagnosis,
image-guided
surgery,
targeted
therapy
mouse
models.
Furthermore,
demonstrate
that
simultaneously
incorporating
mTAF
ketone-containing
ncAA
into
one
via
non-sense
codons
allows
preparation
triconjugate.
Our
results
are
doubly
bio-orthogonal
handles
efficient
scalable
multiconjugates.
Bioconjugate Chemistry,
Journal Year:
2023,
Volume and Issue:
34(11), P. 1951 - 2000
Published: Oct. 11, 2023
Antibody–drug
conjugates
(ADCs)
are
targeted
immunoconjugate
constructs
that
integrate
the
potency
of
cytotoxic
drugs
with
selectivity
monoclonal
antibodies,
minimizing
damage
to
healthy
cells
and
reducing
systemic
toxicity.
Their
design
allows
for
higher
doses
drug
be
administered,
potentially
increasing
efficacy.
They
currently
among
most
promising
classes
in
oncology,
efforts
expand
their
application
nononcological
indications
combination
therapies.
Here
we
provide
a
detailed
overview
recent
advances
ADC
research
consider
future
directions
challenges
promoting
this
platform
widespread
therapeutic
use.
We
examine
data
from
CAS
Content
Collection,
largest
human-curated
collection
published
scientific
information,
analyze
publication
landscape
reveal
exploration
trends
documents
insights
into
area.
also
discuss
evolution
key
concepts
field,
major
technologies,
development
pipelines
company
focuses,
disease
targets,
stages,
investment
trends.
A
comprehensive
concept
map
has
been
created
based
on
Collection.
hope
report
can
serve
as
useful
resource
understanding
current
state
knowledge
field
ADCs
remaining
fulfill
potential.
Acta Pharmaceutica Sinica B,
Journal Year:
2024,
Volume and Issue:
14(5), P. 1965 - 1986
Published: Jan. 20, 2024
Bispecific
antibody‒drug
conjugates
(BsADCs)
represent
an
innovative
therapeutic
category
amalgamating
the
merits
of
(ADCs)
and
bispecific
antibodies
(BsAbs).
Positioned
as
next-generation
ADC
approach,
BsADCs
hold
promise
for
ameliorating
extant
clinical
challenges
associated
with
ADCs,
particularly
pertaining
to
issues
such
poor
internalization,
off-target
toxicity,
drug
resistance.
Presently,
ten
are
undergoing
trials,
initial
findings
underscore
imperative
ongoing
refinement.
This
review
initially
delves
into
specific
design
considerations
BsADCs,
encompassing
target
selection,
antibody
formats,
linker-payload
complex.
Subsequent
sections
delineate
progress
encountered
by
illustrated
through
pertinent
case
studies.
The
amalgamation
BsAbs
ADCs
offers
a
prospective
solution
prevailing
limitations
ADCs.
Nevertheless,
symbiotic
interplay
among
BsAb,
linker,
payload
necessitates
further
optimizations
coordination
beyond
simplistic
"1
+
1"
effectively
surmount
facing
BsADC
domain.
Chemical Society Reviews,
Journal Year:
2024,
Volume and Issue:
53(4), P. 2099 - 2210
Published: Jan. 1, 2024
Recent
tactical
applications
of
prodrugs
as
effective
tools
in
drug
discovery
and
development
to
resolve
issues
associated
with
delivery
lead
candidates
are
reviewed
a
reflection
the
approval
53
during
2012–2022.
Cancer Discovery,
Journal Year:
2024,
Volume and Issue:
14(11), P. 2089 - 2108
Published: Oct. 23, 2024
Abstract
Antibody–drug
conjugates
(ADC)
represent
one
of
the
most
rapidly
expanding
treatment
modalities
in
oncology,
with
11
ADCs
approved
by
FDA
and
more
than
210
currently
being
tested
clinical
trials.
Spanning
over
40
years,
ADC
development
has
enhanced
our
understanding
multifaceted
mechanisms
action
for
this
class
therapeutics.
In
article,
we
discuss
key
insights
into
toxicity,
efficacy,
stability,
distribution,
fate
ADCs.
Furthermore,
highlight
ongoing
challenges
related
to
their
optimization,
rational
sequencing
strategies,
identification
predictive
biomarkers.
Significance:
The
utilization
have
allowed
relevant
improvements
prognosis
multiple
cancer
types.
Concomitantly,
rise
oncology
produced
several
challenges,
including
prediction
activity,
sequence,
minimization
side
effects,
that
still
too
often
resemble
those
cytotoxic
molecule
they
carry.
review,
retrace
years
field
delve
deep
these
complex
therapeutics
reasons
behind
many
achievements
failures
observed
date.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 11, 2025
Synthetic
protein/peptide
modification
is
a
powerful
strategy
for
the
development
of
new
therapeutics
and
tools
chemical
biology.
Accordingly,
synthetic
variant
biological
tyrosine
phosphorylation,
cornerstone
post-translational
landscape,
could
find
widespread
application
in
study
this
fundamental
biochemical
signal.
This
work
describes
mechanistically
novel,
redox-neutral,
photocatalytic
phosphorylation
reaction
via
radical
Arbuzov-type
mechanism.
The
proceeds
with
good
selectivity
di-,
tri-,
oligopeptides
under
mild
conditions
near
neutral
pH,
tolerating
potentially
problematic
functionality.
As
first
reaction,
represents
major
advance
toward
goal
phosphorylation.
Chemical Science,
Journal Year:
2021,
Volume and Issue:
12(41), P. 13613 - 13647
Published: Jan. 1, 2021
The
review
shall
introduce
and
analyse
the
current
developments
in
chemical
modification
of
native
amino
acids
on
peptides
or
proteins
their
applicability
to
ADC
linkers.
Pharmaceuticals,
Journal Year:
2021,
Volume and Issue:
14(5), P. 442 - 442
Published: May 7, 2021
Combining
the
selective
targeting
of
tumor
cells
through
antigen-directed
recognition
and
potent
cell-killing
by
cytotoxic
payloads,
antibody-drug
conjugates
(ADCs)
have
emerged
in
recent
years
as
an
efficient
therapeutic
approach
for
treatment
various
cancers.
Besides
a
number
approved
drugs
already
on
market,
there
is
formidable
follow-up
ADC
candidates
clinical
development.
While
selection
appropriate
antibody
(A)
drug
payload
(D)
dictated
pharmacology
targeted
disease,
one
has
broader
choice
conjugating
linker
(C).
In
present
paper,
we
review
chemistry
ADCs
with
particular
emphasis
medicinal
perspective,
focusing
chemical
methods
that
enable
assembly
from
its
three
components
controlled
release
payload.
