Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
137(3)
Published: Oct. 18, 2024
Abstract
The
glycosylation
of
peptides
and
proteins
can
significantly
impact
their
intrinsic
properties,
such
as
conformation,
stability,
antigenicity,
immunogenicity.
Current
methods
for
preparing
N‐linked
glycopeptides
typically
rely
on
amide
bond
formation,
which
be
limited
by
the
presence
reactive
functional
groups
like
acids
amines.
Late‐stage
functionalization
offers
a
promising
approach
to
obtaining
glycopeptides.
In
this
study,
we
demonstrate
preparation
through
photoredox‐catalyzed
site‐selective
Giese
addition
between
N‐glycosyl
oxamic
acid
containing
dehydroalanine
(Dha)
under
visible
light
conditions.
Unlike
traditional
that
coupling
aspartic
glycosylamine,
utilizes
conjugation
N‐glycosylated
carbamoyl
radicals
with
Dha,
facilitating
straightforward
modification
complex
peptides.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(15), P. 12819 - 12834
Published: July 20, 2024
Synthetic
α-galactosylceramide
(αGalCer)
and
its
analogues
as
powerful
agonists
for
natural
killer
T
(NKT)
cell
manipulation
have
received
significant
attention
in
immunotherapy
adjuvant
development.
However,
identifying
new
potent
NKT
agonists,
especially
those
with
Th1
selectivity
that
promote
anticancer
effects,
remains
a
challenging
task.
In
this
work,
we
introduced
sulfonamide
group
into
the
acyl
chain
of
αGalCer
to
form
additional
hydrogen
bonds
intensify
glycolipid/CD1d
interaction.
Two
compounds
Chinese Journal of Chemistry,
Journal Year:
2024,
Volume and Issue:
42(10), P. 1114 - 1120
Published: Feb. 5, 2024
Comprehensive
Summary
Expressed
protein
ligation
(EPL)
provides
a
powerful
tool
to
access
large‐size
proteins
with
precise
structures.
Existing
methods
for
constructing
the
critical
thioester
EPL
have
predominantly
relied
on
recombinant
intein
fusion
expressed
in
Escherichia
coli
(E.
).
Despite
its
applications,
expression
of
derived
from
eukaryotic
E.
inherently
suffers
limited
solubility,
inactivity
intein,
premature
hydrolysis
and
low
yields.
To
overcome
these
obstacles,
we
present
herein
facile
one‐flask
synthesis
inaccessible
α‐thioester
via
SUMO‐protein‐intein
(SPI)
sandwich
model.
The
utility
SUMO
enhances
yield
prevents
simplifies
purification
process.
internal
Cys
residues
can
be
readily
produced
is
compatible
EPL‐desulfurization
protocol
used
prepare
complex
proteins,
which
otherwise
difficult
obtain
using
traditional
methods.
Its
has
been
highlighted
through
human
granulocyte
colony‐stimulating
factor
(G‐CSF).
This
study
describes
an
efficient
chemical
synthesis
method
of
d
-Dpo4,
a
valuable
enzymatic
tool
producing
mirror-image
DNAs,
using
one-pot
multi-segment
condensation
strategy.
Chinese Journal of Chemistry,
Journal Year:
2024,
Volume and Issue:
42(19), P. 2316 - 2322
Published: May 22, 2024
Comprehensive
Summary
The
strategy
of
removable
glycosylation
modification
was
used
to
overcome
the
low‐efficiency
problem
encountered
in
chemical
synthesis
mirror‐image
D
‐version
immunoglobulin
(Ig)‐like
domain
tropomyosin
receptor
kinase
A
(
lgC
TrkA
),
a
protein
molecule
needed
for
screening
‐peptide
ligands
targeting
this
cell
membrane
receptor.
It
found
that
O‐linked‐β‐
N
‐acetyl‐
‐glucosamine
(O‐GlcNAc)
at
Ser
312
,
or
320
can
significantly
improve
efficiency
and
folding,
while
O‐GlcNAc
330
showed
barely
any
improvement.
This
study
provides
new
example
demonstrating
power
folding
difficult‐to‐obtain
proteins.
also
presents
evidence
different
sites
would
affect
promoted
by
strategy.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(27), P. 18270 - 18280
Published: June 25, 2024
The
receptor
for
advanced
glycation
end
products
(RAGE)
plays
a
crucial
role
in
inflammation-related
pathways
and
various
chronic
diseases.
Despite
the
recognized
significance
of
N-glycosylation
ligand-binding
V
domain
(VD)
RAGE,
comprehensive
understanding
site-activity
structure-activity
relationships
is
lacking
due
to
challenges
obtaining
homogeneous
glycoprotein
samples
through
biological
expression.
Here,
we
combined
chemical
chemoenzymatic
approaches
synthesize
RAGE-VD
its
congeners
with
Asn3-glycosylation
by
incorporating
precise
N-glycan
structures.
Evaluation
these
revealed
that,
comparison
other
forms,
α2,6-sialylated
at
Asn3
site
results
more
potent
inhibition
HMGB1-induced
nuclear
factor-κB
(NF-κB)
expression
RAGE-overexpressing
cells.
Hydrogen/deuterium
exchange-mass
spectrum
analysis
sialylated
RAGE-VD-induced
interaction
region
within
HMGB1.
Conversely,
VD
has
negligible
effects
on
RAGE-VD/S100B
interactions.
This
study
established
an
approach
accessing
homogeneously
glycosylated
explored
modulatory
interactions
between
ligand
proteins.
Organic & Biomolecular Chemistry,
Journal Year:
2024,
Volume and Issue:
22(19), P. 3986 - 3994
Published: Jan. 1, 2024
Sulfated
mannuronate
glycans
with
up
to
17
sulfation
sites
were
synthesized
using
a
microwave-assisted
approach
and
evaluated
as
inhibitors
against
SARS-CoV-2.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
64(3)
Published: Oct. 18, 2024
Abstract
The
glycosylation
of
peptides
and
proteins
can
significantly
impact
their
intrinsic
properties,
such
as
conformation,
stability,
antigenicity,
immunogenicity.
Current
methods
for
preparing
N‐linked
glycopeptides
typically
rely
on
amide
bond
formation,
which
be
limited
by
the
presence
reactive
functional
groups
like
acids
amines.
Late‐stage
functionalization
offers
a
promising
approach
to
obtaining
glycopeptides.
In
this
study,
we
demonstrate
preparation
through
photoredox‐catalyzed
site‐selective
Giese
addition
between
N‐glycosyl
oxamic
acid
containing
dehydroalanine
(Dha)
under
visible
light
conditions.
Unlike
traditional
that
coupling
aspartic
glycosylamine,
utilizes
conjugation
N‐glycosylated
carbamoyl
radicals
with
Dha,
facilitating
straightforward
modification
complex
peptides.
Organic & Biomolecular Chemistry,
Journal Year:
2024,
Volume and Issue:
22(18), P. 3584 - 3588
Published: Jan. 1, 2024
Asp-based
lactam
cyclic
peptides
are
considered
promising
drug
candidates.
However,
using
Fmoc
solid-phase
peptide
synthesis
(Fmoc-SPPS)
for
these
also
causes
aspartimide
formation,
resulting
in
low
yields
or
even
failure
to
obtain
the
target
peptides.
Here,
we
developed
a
diaminodiacid
containing
an
amide
bond
as
β-carboxyl-protecting
group
Asp
avoid
formation.
The
practicality
of
this
has
been
illustrated
by
cyclo[Lys9,Asp13]
KIIIA7-14
and
1Y.
