Comprehensive synthesis and anticoagulant evaluation of a diverse fucoidan library
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: May 10, 2025
Fucoidan,
a
sulfated
glycan
derived
from
brown
algae,
has
garnered
significant
attention
for
its
anticoagulant
properties.
However,
the
structural
complexity
and
heterogeneity
of
naturally
extracted
fucoidan
have
hindered
comprehensive
understanding
structure-activity
relationship,
limiting
development
fucoidan-based
drugs.
To
address
this
challenge,
we
synthesize
diverse
library
58
distinct
fucoidans
with
multiple
contiguous
1,2-cis
glycosidic
bonds,
ranging
disaccharides
to
dodecasaccharides,
using
highly
efficient
preactivation-based
one-pot
glycosylation
strategy.
This
includes
compounds
various
sulfation
patterns
(2,3-O-di-,
3,4-O-di-,
2,3,4-O-tri-sulfation)
encompassing
nearly
all
possible
structures.
In
vitro
assays
demonstrate
that
both
molecular
size
degree
play
crucial
roles
in
potency.
Notably,
29,
30,
37,
significantly
prolong
human
plasma
activated
partial
thromboplastin
time
(APTT),
comparable
effect
enoxaparin,
without
affecting
prothrombin
(PT)
or
thrombin
(TT).
selective
inhibition
intrinsic
coagulation
pathway
suggests
reduced
risk
bleeding,
highlighting
therapeutic
potential
these
as
safer
agents.
Language: Английский
Investigation into the Binding Domains of Platelet Factor 4 Unlocks New Avenues for the Design and Synthesis of Selective Sulfated Pseudo-Tetrasaccharide Aminoglycoside Ligands
European Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
295, P. 117792 - 117792
Published: May 21, 2025
Language: Английский