bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 9, 2023
Abstract
The
Tat
pathway
is
essential
for
photosynthetic
protein
transport
across
plant
thylakoid
membranes
and
also
ubiquitous
throughout
prokaryotes
archaea.
unique
amongst
translocation
pathways
as
it
specializes
in
transporting
folded
proteins
driven
by
a
proton
motive
force.
Mechanistic
details
of
the
actual
step
(s)
remain
elusive.
Here,
we
show
that
membrane
thinning
stimulates
and,
conversely,
strengthening
abolishes
transport.
We
draw
parallels
from
mechanism
to
cell
penetrating
peptides
propose
pore
could
be
toroidal
shape
lined
lipids,
those
formed
peptides.
Significance
Statement
Protein
significant
cellular
activity
both
eukaryotes.
operates
bacteria,
archaea,
chloroplasts,
mitochondria.
Its
action
has
been
difficult
decipher,
but
recent
evidence
suggests
does
not
use
conical
proteinaceous
channel.
Instead,
suggested
translocate
through
lipid-lined
pores
set
up
thinning.
This
work
supports
hypothesis
showing
membrane-thinning
cell-penetrating
stimulate
chloroplasts
bacterial
plasma
membranes,
stabilization
blocks
pathway.
believe
this
most
direct
date
operating
Natural Product Reports,
Год журнала:
2023,
Номер
41(3), С. 331 - 346
Опубликована: Сен. 25, 2023
Covering:
2018
to
Jun
of
2023The
efficiency
traditional
antibiotics
has
been
undermined
by
the
proliferation
antibiotic-resistant
pathogenic
microorganisms,
necessitating
pursuit
innovative
therapeutic
agents.
Antimicrobial
peptides
(AMPs),
which
are
part
host
defence
found
ubiquitously
in
nature,
exhibiting
a
wide
range
activity
towards
bacteria,
fungi,
and
viruses,
offer
highly
promising
candidate
solution.
The
efficacy
AMPs
can
frequently
be
augmented
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 5, 2025
The
successful
approval
of
peptide-based
drugs
can
be
attributed
to
a
collaborative
effort
across
multiple
disciplines.
integration
novel
drug
design
and
synthesis
techniques,
display
library
technology,
delivery
systems,
bioengineering
advancements,
artificial
intelligence
have
significantly
expedited
the
development
groundbreaking
drugs,
effectively
addressing
obstacles
associated
with
their
character,
such
as
rapid
clearance
degradation,
necessitating
subcutaneous
injection
leading
increasing
patient
discomfort,
ultimately
advancing
translational
research
efforts.
Peptides
are
presently
employed
in
management
diagnosis
diverse
array
medical
conditions,
diabetes
mellitus,
weight
loss,
oncology,
rare
diseases,
additionally
garnering
interest
facilitating
targeted
platforms
advancement
vaccines.
This
paper
provides
an
overview
present
market
clinical
trial
progress
therapeutics,
platforms,
It
examines
key
areas
through
literature
analysis
emphasizes
structural
modification
principles
well
recent
advancements
screening,
design,
technologies.
accelerated
including
peptide-drug
complexes,
new
vaccines,
innovative
diagnostic
reagents,
has
potential
promote
era
precise
customization
disease
therapeutic
schedule.
Computational and Structural Biotechnology Journal,
Год журнала:
2024,
Номер
23, С. 972 - 981
Опубликована: Фев. 12, 2024
Antimicrobial
peptides
(AMPs)
are
molecules
found
in
most
organisms,
playing
a
vital
role
innate
immune
defense
against
pathogens.
Their
mechanism
of
action
involves
the
disruption
bacterial
cell
membranes,
causing
leakage
cellular
contents
and
ultimately
leading
to
death.
While
AMPs
typically
lack
defined
structure
solution,
they
often
assume
conformation
when
interacting
with
membranes.
Given
this
structural
flexibility,
we
investigated
whether
intrinsically
disordered
regions
(IDRs)
AMP-like
properties
could
exhibit
antimicrobial
activity.
We
tested
14
from
different
IDRs
predicted
have
activity
that
nearly
all
them
did
not
display
anticipated
effects.
These
failed
adopt
secondary
had
compromised
membrane
interactions,
resulting
hypothesize
evolutionary
constraints
may
prevent
folding,
even
membrane-like
environments,
limiting
their
potential.
Moreover,
our
research
reveals
current
predictors
fail
accurately
capture
features
dealing
unstructured
sequences.
Hence,
results
presented
here
far-reaching
implications
for
designing
improving
strategies
therapies
infectious
diseases.
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2025,
Номер
unknown, С. 1 - 18
Опубликована: Янв. 31, 2025
Antimicrobial
and
plant
defence
elicitor
peptides
have
received
attention
on
last
decades
as
novel
tools
to
combat
bacterial
diseases.
We
previously
reported
a
library
of
peptide
conjugates
resulting
from
the
combination
an
antimicrobial
(BP16,
BP143,
BP387
or
BP475)
sequence
(flg15,
BP13,
Pep13
PIP1).
From
this
library,
we
selected
set
14
including
both
highly
poorly
active
sequences
performed
structure-activity
relationship
study
by
NMR
MD
simulations.
Analysis
their
structure
in
30%
TFE-d3
zwitterionic
DPC-d38
anionic
SDS-d25
micelles
showed
that
presence
α-helix
fragment
together
with
flexible
random
coil
can
be
related
high
antibacterial
activity
low
hemolysis.
In
contrast,
rigid
were
hemolytic.
PRE-NMR
experiments
MnCl2
16-DSA
revealed
flg15-BP475
BP100-Pep13
interacted
stronger
than
BP13-BP16.
two
former
interaction
took
place
through
region.
GaMD
simulations
conducted
membranes
composed
DPPG
lipids,
after
its
electrostatic
interaction,
flipped
hydrophobic
residues
faced
membrane
triggering
insertion
also
causing
thinning.
Thus,
flexibility
moderate
cationicity
seem
crucial
for
biological
activity.
These
findings
help
establish
guidelines
future
rational
design
BP100
derivatives.
ACS Infectious Diseases,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 24, 2025
Multidrug-resistant
bacteria
(MDR)
have
become
a
global
threat,
impairing
positive
outcomes
in
many
cases
of
infectious
diseases.
Treating
bacterial
infections
with
antibiotic
monotherapy
has
huge
challenge
modern
medicine.
Although
conventional
antibiotics
can
be
efficient
against
bacteria,
there
is
still
need
to
develop
antimicrobial
agents
that
act
MDR
bacteria.
Bioactive
peptides,
particularly
effective
specific
types
are
recognized
for
their
selective
and
action
microorganisms
and,
at
the
same
time,
relatively
safe
well
tolerated.
Therefore,
growing
number
works
proposed
use
peptides
(AMPs)
synergism
commercial
as
an
alternative
therapeutic
strategy.
This
review
provides
overview
critical
parameters
using
AMPs
addressing
strengths
weaknesses
this
combination
therapy
vitro
vivo
models
infection.
We
also
cover
challenges
perspectives
approach
clinical
practice
advantages
applying
artificial
intelligence
strategies
predict
most
promising
therapies
between
antibiotics.
