Structural Unfolding of G-Quadruplexes: From Small Molecules to Antisense Strategies
Giorgia Fracchioni,
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Sabrina Vailati,
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Marta Grazioli
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et al.
Molecules,
Journal Year:
2024,
Volume and Issue:
29(15), P. 3488 - 3488
Published: July 25, 2024
G-quadruplexes
(G4s)
are
non-canonical
nucleic
acid
secondary
structures
that
have
gathered
significant
interest
in
medicinal
chemistry
over
the
past
two
decades
due
to
their
unique
structural
features
and
potential
roles
a
variety
of
biological
processes
disorders.
Traditionally,
research
efforts
focused
on
stabilizing
G4s,
while
recent
years,
attention
has
progressively
shifted
G4
destabilization,
unveiling
new
therapeutic
perspectives.
This
review
provides
an
in-depth
overview
advances
development
small
molecules,
starting
with
controversial
role
TMPyP4.
Moreover,
we
described
effective
metal
complexes
addition
G4-disrupting
molecules
as
well
good
ligands
can
destabilize
G4s
response
external
stimuli.
Finally,
presented
antisense
strategies
promising
approach
for
destabilizing
particular
focus
2'-OMe
oligonucleotide,
peptide
acid,
locked
acid.
Overall,
this
emphasizes
importance
understanding
dynamics
ongoing
develop
selective
G4-unfolding
modulate
function
potential.
Language: Английский
ESCMID's World Antimicrobial Resistance Awareness Week 2024: Key Takeaways and Path Forward
Tomislav Meštrović,
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Giorgia Caruana,
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Christian Kraef
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et al.
CMI Communications,
Journal Year:
2025,
Volume and Issue:
unknown, P. 105071 - 105071
Published: March 1, 2025
Language: Английский
Dibenzoacridinium Derivatives as a New Class of G-Quadruplex Ligands with Antiviral Properties
Amani Kabbara,
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Corinne Buré,
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Aurore Guédin
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et al.
Published: Jan. 1, 2025
Language: Английский
Targeting Mycobacterium tuberculosis Parallel G-Quadruplex Motifs with Aminoglycosides Neomycin and Streptomycin: Spectroscopic and Calorimetric Aspects
The Journal of Physical Chemistry B,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 4, 2025
Mycobacterium
tuberculosis
(Mtb)
contains
potential
G-quadruplex
(PGQ)
motifs
in
the
genes
espK
and
cyp51,
which
are
crucial
for
bacteria's
virulence
within
host
cells.
Aminoglycoside
molecules
commonly
used
as
antibiotics
ribosomal
targets.
This
study
provides
insight
into
interactions
between
these
aminoglycosides
Mtb-PGQ
sequences
(espK
cyp51),
shedding
light
on
structural
thermodynamic
dynamics
of
their
binding.
demonstrates
stability,
affinity,
conformation
presence
neomycin
streptomycin.
Ultraviolet-visible
spectroscopy
(UV–vis),
circular
dichroism
(CD),
CD
thermal
melting,
isothermal
titration
calorimetry
(ITC),
fluorescence
intercalator
displacement
(FID)
assays
were
to
comprehensively
examine
interactions.
Our
results
reveal
that
with
Mtb-PGQexhibits
hypochromism
accompanied
by
a
4–5
nm
red
shift
UV–visible
absorption
titration,
whereas
streptomycin
exhibits
hypochromic
without
changes
maximum
wavelength.
Notably,
shows
nonlinear
binding
isotherm,
suggesting
involvement
more
than
one
process
formation
neomycin.Mtb-PGQ
complexes.
Scatchard
plot
analysis
indicates
higher
affinity
values
compared
weaker
studies
decreases
ellipticity
while
retaining
parallel
topology,
ultimately
enhancing
stability
both
cyp51.
In
contrast,
destabilizes
ITC
reveals
strongest
relative
order
being
NEO-cyp51
>
NEO-espk
STR-cyp51
STR-espk.
Moreover,
possesses
unique
dual
mode
through
grooves
well
stacking.
FID
further
confirm
lower
DC50
value
streptomycin,
is
strong
displacer
thiazole
orange.
Thus,
show
amino
groups
selectively
recognizes
cyp51
over
espK.
Language: Английский
Oligostyrylbenzene Derivatives with Antiparasitic and Antibacterial Activity as Potent G-Quadruplex Ligands
Molecules,
Journal Year:
2024,
Volume and Issue:
29(24), P. 5875 - 5875
Published: Dec. 12, 2024
G-quadruplexes
(G4s)
are
non-canonical
secondary
structures
that
play
a
crucial
role
in
the
regulation
of
genetic
expression.
This
study
explores
interaction
between
G4s
and
small
family
oligostyrylbenzene
(OSB)
derivatives,
characterized
by
tris(styryl)benzene
tetrastyrylbenzene
backbones,
functionalized
with
either
trimethylammonium
or
1-methylpyridinium
groups.
Initially
identified
as
DNA
ligands,
these
OSB
derivatives
have
now
been
recognized
potent
G4
binders,
surpassing
binding
affinity
commercially
available
ligands
such
pyridostatin
displaying
good
selectivity
for
over
duplex
DNA.
Furthermore,
1
2
demonstrated
significant
antiparasitic
activity
against
bloodstream
forms
T.
brucei
extracellular
L.
major,
high
indices
when
compared
to
MRC-5
healthy
control
cells.
Derivatives
exhibited
moderate
biocidal
effects
range
Gram-positive
Gram-negative
bacterial
strains.
Notably,
synergistic
antibacterial
effect
was
observed
compounds
were
combined
traditional
antibiotics,
particularly
Acinetobacter
baumannii,
highlighting
their
potential
utility
addressing
drug-resistant
infections.
The
differences
bioactivity
among
can
be
attributed
variations
cellular
uptake,
proved
flow
cytometry
analysis.
suggests
degree
internalization
plays
pivotal
efficacy.
Language: Английский
Molecular Modelling and Investigation of Bioactive Stable DNA G-Quadruplex d(G4T4G4) under Different Physiological Conditions using Molecular Dynamics Simulation
Prabha Materials Science Letters,
Journal Year:
2024,
Volume and Issue:
4(1), P. 107 - 118
Published: Dec. 27, 2024
We
are
reporting
a
molecular
dynamics
study
on
the
structure
and
conformation
of
DNA
quadruplex.
The
single
molecule
quadruplex's
coordinates
were
obtained
modeled
using
PDB
ID
1d59.
simulation's
sequence
is
d(GGGGTTTTGGGG).
In
beginning,
two
hairpin
structures
constructed
with
loops
holding
thymine
residues
at
either
end,
forming
four-stranded
helical
structure.
cyclic
hydrogen
bonds
created
by
kept
guanine
all
four
strands
in
one
plane.
was
subjected
to
simulation
for
100ns
periodic
intervals
10ns,
dynamical
pathway's
trajectory
examined.
deviations
fluctuations
viz.
RMSD,
RMSF
Rg
plots
analyzed,
shape
time-evolved
outcome
compared
crystal
Our
findings
reveal
few
peculiar
properties
which
we
have
discussed
this
paper.
helix
axis
torsion
angle
parameters
calculated.
results
interpretation
give
idea
about
quadruplex
interaction
external
agents
inspire
do
further
research
telomeric
regions
living
chromosomes.
Language: Английский