Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
176, С. 116910 - 116910
Опубликована: Июнь 8, 2024
Therapeutic
proteins
provided
new
opportunities
for
patients
and
high
sales
volumes.
However,
they
are
formulated
extracellular
targets.
The
lipophilic
barrier
of
the
plasma
membrane
renders
vast
array
intracellular
targets
out
reach.
Peptide-based
delivery
systems,
namely
cell-penetrating
peptides
(CPPs),
have
few
safety
concerns,
low
immunogenicity,
with
control
over
administered
doses.
This
study
investigates
CPP-based
protein
systems
by
classifying
them
into
CPP-protein
"covalent
conjugation"
CPP:
"non-covalent
complexation"
categories.
Covalent
conjugates
ensure
proximity
CPP
to
cargo,
which
can
improve
cellular
uptake
endosomal
escape.
We
will
discuss
various
aspects
covalent
through
non-cleavable
(stable)
or
cleavable
bonds.
Non-cleavable
produced
recombinant
DNA
technology
express
complete
fusion
in
a
host
cell
chemical
ligation
protein,
ensures
stability
during
process.
bonds
classified
pH-sensitive
redox-sensitive
bonds,
enzyme-cleavable
physical
stimuli
linkers
(light
radiation,
ultrasonic
waves,
thermo-responsive).
highlighted
key
characteristics
non-covalent
complexes
electrostatic
hydrophobic
interactions
preserve
conformational
integrity
cargo.
CPP-mediated
complexation,
such
as
zippers,
adaptor
methods,
avidin-biotin
technology,
featured.
Conclusively,
complexation
methods
appropriate
when
number
samples
be
screened.
In
contrast,
biological
activity
is
critical
compartment,
conjugation
protocols
preferred.
ACS Central Science,
Год журнала:
2024,
Номер
10(5), С. 1033 - 1043
Опубликована: Апрель 17, 2024
Thiol-mediated
uptake
(TMU)
is
an
intriguing
enigma
in
current
chemistry
and
biology.
While
the
appearance
of
cell-penetrating
activity
upon
attachment
cascade
exchangers
(CAXs)
has
been
observed
by
many
increasingly
being
used
practice,
molecular
basis
TMU
essentially
unknown.
The
objective
this
study
was
to
develop
a
general
protocol
decode
dynamic
covalent
networks
that
presumably
account
for
TMU.
Uptake
inhibition
patterns
obtained
from
removal
exchange
partners
either
protein
knockdown
or
alternative
inhibitors
are
aligned
with
original
generated
CAX
transporters
functions
(here
cell
motility).
These
inclusive
reveal
four
most
significant
CAXs
known
today
enter
cells
along
three
almost
orthogonal
pathways.
Epidithiodiketopiperazines
(ETP)
preferably
integrins
disulfide
isomerases
(PDIs),
benzopolysulfanes
(BPS)
different
PDIs,
PDIA3,
asparagusic
acid
(AspA),
antisense
oligonucleotide
phosphorothioates
(OPS)
transferrin
receptor
can
be
activated
PDIs
their
respective
inhibitors.
findings
provide
solid
understand
use
enable
prevent
entry
into
cells.
Chemical Reviews,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 17, 2025
The
nascent
field
of
targeted
protein
degradation
(TPD)
could
revolutionize
biomedicine
due
to
the
ability
degrader
molecules
selectively
modulate
disease-relevant
proteins.
A
key
limitation
broad
application
TPD
is
its
dependence
on
small-molecule
ligands
target
proteins
interest.
This
leaves
unstructured
or
those
lacking
defined
cavities
for
binding
out
scope
many
technologies.
use
proteins,
peptides,
and
nucleic
acids
(otherwise
known
as
"biologics")
protein-targeting
moieties
in
degraders
addresses
this
limitation.
In
following
sections,
we
provide
a
comprehensive
critical
review
studies
that
have
used
peptides
mediate
hence
functional
control
otherwise
challenging
targets.
We
describe
existing
platforms
protein/peptide-based
ligand
identification
drug
delivery
systems
might
be
exploited
biologic-based
degraders.
Throughout
Review,
underscore
successes,
challenges,
opportunities
using
protein-based
chemical
biology
tools
spur
discoveries,
elucidate
mechanisms,
act
new
therapeutic
modality.
ACS Bio & Med Chem Au,
Год журнала:
2025,
Номер
5(2), С. 268 - 282
Опубликована: Фев. 27, 2025
Biologics
such
as
proteins,
peptides,
and
oligonucleotides
are
powerful
ligands
to
modulate
challenging
drug
targets
that
lack
readily
accessible
"ligandable"
pockets.
However,
the
limited
membrane
permeance
of
biologics
severely
restricts
their
intracellular
applications.
Moreover,
different
cell
types
may
exhibit
varying
levels
impermeability,
some
delivery
vehicles
might
be
more
sensitive
this
variance.
Erythroid
lineage
cells
especially
deliver
cargo
because
unique
cytoskeleton
absence
endocytosis
in
mature
erythrocytes.
We
recently
employed
a
permeant
miniature
protein
bioPROTACs
human
umbilical
cord
blood
derived
erythroid
progenitor
(HUDEP-2)
primary
hematopoietic
stem
(CD34+)
(Shen
et
al.,
ACS
Cent.
Sci.
2022,
8,
1695−1703).
While
successful,
low
efficiency
cell-type
specificity
limit
use
vivo.
In
work,
we
thoroughly
evaluated
performance
various
reported
penetrating
peptides
(CPPs),
CPP
additives,
bacterial
toxins,
contractile
injection
systems
for
ability
precursor
cells.
also
explored
how
targeting
receptors
enriched
on
surface
improve
efficiencies
specificities
these
vehicles.
Our
results
reveal
certain
improved
when
directed
while
others
do
not
benefit
from
strategy.
Together,
findings
advance
our
understanding
illustrate
intricacies
cell-surface
receptor
targeting.
Brain Research,
Год журнала:
2024,
Номер
1838, С. 148987 - 148987
Опубликована: Май 6, 2024
Dynamin
is
a
microtubule
(MT)
binding
protein
playing
key
role
in
vesicle
endocytosis.
In
brain
slice
model,
tau
loaded
presynaptic
terminals
assembles
MTs,
thereby
impairing
endocytosis
via
depletion
of
cytosolic
dynamin.
The
peptide
PHDP5,
derived
from
the
pleckstrin
homology
domain
dynamin
1,
inhibits
dynamin-MT
interaction
and
rescues
synaptic
transmission
impaired
by
when
co-loaded
terminals.
We
tested
whether
vivo
administration
PHDP5
could
rescue
their
learning/memory
deficits
observed
Alzheimer's
disease
(AD)
model
mice.
A
modified
incorporating
cell-penetrating
(CPP)
FITC
fluorescent
marker
was
delivered
intranasally
to
Tau609
transgenic
(Tg)
3xTg-AD
FITC-positive
puncta
were
hippocampus
mice
infused
with
or
scrambled
(SPHDP5)
peptide,
but
not
saline-infused
controls.
Morris
water
maze
(MWM)
test
for
spatial
learning/memory,
AD
treated
FITC-PHDP5-CPP
showed
prominent
improvements
learning
memory,
performing
close
level
WT
control.
contrast,
construct
(FITC-SPHDP5-CPP)
no
significant
improvement.
conclude
that
can
be
candidate
human
therapy.
