Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion
Beilstein Journal of Organic Chemistry,
Год журнала:
2025,
Номер
21, С. 736 - 748
Опубликована: Апрель 8, 2025
Carbohydrate
recognition
is
fundamental
to
a
plethora
of
cellular
processes
and
hence
the
elucidation
structural
determinants
process
prerequisite
for
understanding
manipulating
carbohydrate-protein
interactions,
such
as
in
inhibition
carbohydrate-specific
bacterial
adhesion.
For
receptor
binding,
glycoligands
have
be
properly
oriented
three-dimensional
space
additionally,
secondary
interactions
exerted
by
multivalent
an
effect
on
affinity.
A
recently
introduced
orthogonally
photoswitchable
heterobivalent
azobenzene
Glc/Man
glycocluster
was
utilized
examine
these
aspects
carbohydrate
adhesion-inhibition
assay.
The
measured
results
were
systematically
contextualized
employing
new
reference
compounds
respective
homobivalent
Man/Man
glycocluster.
An
in-depth
study
comprising
analysis
photochromic
properties
potential
inhibitors
adhesion
synthetic
glycophotoswitches
their
different
isomeric
states
led
insights
into
role
ligand
orientation
recognition.
experimental
underpinned
molecular
modeling.
Язык: Английский
Bioactive Polymeric Scaffolds: Multivalent Functionalization by Thermal Azide–Alkyne Cycloaddition with Alkynyl Dicarbamates
Biomacromolecules,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 26, 2025
Multivalency
enables
interactions
with
higher
affinities
and
specificities
than
monovalent
interactions.
The
strategy
exploited
by
nature
to
modulate
biorecognition
has
inspired
the
design
of
multivalent
conjugates
therapeutic
properties.
However,
chemical
functionalization
often
requires
coupling
agents,
additives,
or
metal
catalysts
that
complicate
isolation
purification.
Herein,
azide–alkyne
cycloaddition
(AAC)
alkynyl
dicarbamates
(Alk-R)
is
presented
as
a
flexible,
reliable,
atom-economical,
user-friendly
for
polymeric
scaffolds.
Alk-R
functionalized
biologically
relevant
ligands
have
been
prepared
used
AAC
azide-bearing
dendrimers
block
copolymers.
resulting
polymers
double
multivalency
reveal
platform
development
bioinspired
functional
systems
promising
applications
in
drug
delivery:
copolymer
micelles
multifunctional
nanocarriers
synergistically
integrated
probes-ligands-drugs.
extension
this
other
scaffolds
expected
open
up
wide
range
diagnostic
opportunities.
Язык: Английский
Chemoenzymatic synthesis of sialylated and fucosylated mucin analogs reveals glycan-dependent effects on protein conformation and degradation
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 17, 2025
Abstract
Mucin
proteins
are
essential
for
life
but
challenging
to
study
due
their
complex
glycosylation
patterns.
Synthetic
mimics
have
become
vital
tools
understanding
and
modulating
the
roles
of
mucins
in
human
health
disease.
We
developed
a
chemoenzymatic
approach
prepare
polypeptide-based
synthetic
displaying
variety
glycans
with
native
linkages
orientations.
By
combining
polymerization
glycosylated
amino
acid
N
-carboxyanhydrides
enzymatic
sialylation
fucosylation,
we
produced
tunable
panel
mucins.
These
polymers
were
recognized
by
natural
glycan-binding
glycan-degrading
enzymes,
providing
insights
into
structural
preferences
these
proteins.
Glycan-
linkage-dependent
effects
on
proteolysis
observed.
Further,
investigation
influence
peptide
backbone
secondary
structure
revealed
that
both
linkage
at
Ser
vs.
Thr
profound
hierarchical
conformation.
Overall,
our
methodology
offers
versatile
exploring
diverse
glycobiology
Язык: Английский
Comparative anatomy of siphophage tails before and after interaction with their receptor
Current Opinion in Structural Biology,
Год журнала:
2025,
Номер
92, С. 103045 - 103045
Опубликована: Апрель 24, 2025
Язык: Английский
Overcoming the novel glycan-lectin checkpoints in tumor microenvironment for the success of the cross-presentation-based immunotherapy
Mannat Jain,
Isha M. Jadhav,
Suyash Vinayak Dangat
и другие.
Biomaterials Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
(a)
Two
primary
mechanisms
for
cross-presentation
of
internalized
antigens:
cytosolic
and
vacuolar
pathways.
(b)
To
enhance
antigen
presentation
generate
T
cell
responses,
glycans
are
multivalently
presented
on
a
range
nanocarrier
systems.
Язык: Английский
Multivalent Siglec Ligands
Carbohydrate Research,
Год журнала:
2025,
Номер
unknown, С. 109520 - 109520
Опубликована: Май 1, 2025
Язык: Английский
Exploring Multivalent Architectures for Binding and Stabilization of N-Acetylgalactosamine 6-Sulfatase
Molecules,
Год журнала:
2025,
Номер
30(10), С. 2222 - 2222
Опубликована: Май 20, 2025
Morquio
A
syndrome
is
a
lysosomal
disorder
caused
by
the
deficiency
of
enzyme
N-acetylgalactosamine
6-sulfatase
(GALNS,
EC
3.1.6.4).
Currently,
replacement
therapy
(ERT)
used
to
treat
through
infusion
recombinant
VIMIZIM®
(elosulfase
alfa,
BioMarin).
Unfortunately,
exhibits
low
conformational
stability
in
vivo.
promising
approach
address
this
issue
coadministration
human
GALNS
(rhGALNS)
with
pharmacological
chaperone
(PC),
molecule
that
selectively
binds
misfolded
protein,
stabilizes
its
conformation,
and
assists
restoration
impaired
function.
We
report
work
synthesis
library
multivalent
glycomimetics
exploiting
copper(I)-catalyzed
azide-alkyne
cycloaddition
(CuAAC)
reaction
between
several
dendrimeric
scaffolds
armed
terminal
alkynes
azido
ending
iminosugars
different
structures
(pyrrolidines,
piperidines,
pyrrolizidines)
or
simple
carbohydrates
as
bioactive
units.
The
biological
evaluation
identified
pyrrolidine-based
nonavalent
dendrimers
1
36
most
compounds,
able
both
bind
native
IC50
micromolar
range
act
stabilizers
toward
rhGALNS
thermal
denaturation
study,
thus
identifying
compounds
for
combined
PC/ERT
therapy.
Язык: Английский
Roles for Siglec-glycan interactions in regulating immune cells
Seminars in Immunology,
Год журнала:
2024,
Номер
77, С. 101925 - 101925
Опубликована: Дек. 19, 2024
Язык: Английский
Multivalent GCase Enhancers: Synthesis and Evaluation of Glyco-Gold Nanoparticles Decorated with Trihydroxypiperidine Iminosugars
Bioconjugate Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 19, 2024
The
present
study
reports
the
preparation
of
first
multivalent
iminosugars
built
onto
a
glyco-gold
nanoparticle
core
(glyco-AuNPs)
capable
stabilizing
or
enhancing
activity
lysosomal
enzyme
GCase,
which
is
defective
in
Gaucher
disease.
An
N-nonyltrihydroxypiperidine
was
selected
as
bioactive
iminosugar
unit
and
further
functionalized,
via
copper-catalyzed
alkyne–azide
cycloaddition,
with
thiol-ending
linker
that
allowed
conjugation
to
gold
core.
These
ligands
were
obtained
either
linear
monomeric
dendritic
trimeric
arrangement
iminosugar.
concentration
on
surface
modulated
different
amounts
glucoside
bearing
short
spacer
inner
ligand.
new
mixed-ligand
coated
glyco-AuNPs
fully
characterized,
those
highest
colloidal
stability
aqueous
medium
subjected
biological
evaluation.
Glyco-AuNPs
units
showed
ability
stabilize
recombinant
GCase
thermal
denaturation
assay,
while
able
enhance
mutant
patient's
fibroblasts
by
1.9-fold
at
2.2
μM.
Язык: Английский
Multifunctional Theranostic Glyconanoprobes for Synergistic Eradication of Breast Cancer
Journal of Materials Chemistry B,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 24, 2024
The
development
of
multifunctional
theranostic
glyconanoprobes
for
breast
cancer
is
distinguished
by
their
tumor-targeting
capability
and
enhanced
antitumor
efficacy,
achieved
through
synergistic
chemo-gene
photothermal
therapy.
Язык: Английский