Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(16)
Published: Feb. 20, 2024
Abstract
α‐Ketoaldehydes
play
versatile
roles
in
the
ubiquitous
natural
processes
of
protein
glycation.
However,
leveraging
reactivity
α‐ketoaldehydes
for
biomedical
applications
has
been
challenging.
Previously,
with
guanidine
harnessed
to
design
probes
labeling
Arg
residues
on
proteins
an
aqueous
medium.
Herein,
a
highly
effective,
broadly
applicable,
and
operationally
simple
protocol
stapling
native
peptides
by
crosslinking
two
amino
groups
through
diverse
imidazolium
linkers
various
α‐ketoaldehyde
reagents
is
described.
The
use
hexafluoroisopropanol
as
solvent
facilitates
rapid
clean
reactions
under
mild
conditions
enables
unique
selectivity
Lys
over
Arg.
naturally
occurring
GOLD/MOLD
have
expanded
encompass
wide
range
modified
gly
o
xal‐
l
ysine
d
imer
(OLD)
linkers.
In
proof‐of‐concept
trial,
these
modular
enabled
convenient
two‐round
strategy
streamline
structure–activity
relationship
(SAR)
study
wasp
venom
peptide
anoplin,
leading
enhanced
biological
activities.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(16)
Published: Feb. 20, 2024
α-Ketoaldehydes
play
versatile
roles
in
the
ubiquitous
natural
processes
of
protein
glycation.
However,
leveraging
reactivity
α-ketoaldehydes
for
biomedical
applications
has
been
challenging.
Previously,
with
guanidine
harnessed
to
design
probes
labeling
Arg
residues
on
proteins
an
aqueous
medium.
Herein,
a
highly
effective,
broadly
applicable,
and
operationally
simple
protocol
stapling
native
peptides
by
crosslinking
two
amino
groups
through
diverse
imidazolium
linkers
various
α-ketoaldehyde
reagents
is
described.
The
use
hexafluoroisopropanol
as
solvent
facilitates
rapid
clean
reactions
under
mild
conditions
enables
unique
selectivity
Lys
over
Arg.
naturally
occurring
GOLD/MOLD
have
expanded
encompass
wide
range
modified
glyoxal-lysine
dimer
(OLD)
linkers.
In
proof-of-concept
trial,
these
modular
enabled
convenient
two-round
strategy
streamline
structure-activity
relationship
(SAR)
study
wasp
venom
peptide
anoplin,
leading
enhanced
biological
activities.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(10), P. 6773 - 6783
Published: Feb. 29, 2024
The
past
decade
has
seen
a
remarkable
growth
in
the
number
of
bioconjugation
techniques
chemistry,
biology,
material
science,
and
biomedical
fields.
A
core
design
element
technology
is
chemical
reaction
that
can
form
covalent
bond
between
protein
interest
labeling
reagent.
Achieving
chemoselective
aqueous
media
challenging,
especially
for
generally
less
reactive
amino
acid
residues,
such
as
tryptophan.
We
present
here
development
tryptophan-selective
methods
through
ultrafast
Lewis
acid-catalyzed
reactions
hexafluoroisopropanol
(HFIP).
Structure–reactivity
relationship
studies
have
revealed
combination
thiophene
ethanol
moieties
to
give
suitable
reagent
this
process,
which
enables
modification
peptides
proteins
an
extremely
rapid
unencumbered
by
noticeable
side
reactions.
capability
method
also
facilitated
radiofluorination
application
well
antibody
functionalization.
Enhancement
α-helix
HFIP
leads
its
compatibility
with
certain
protein,
report
demonstrates
further
stabilization
strategy
achieved
addition
ionic
liquid
medium.
nonaqueous
approaches
allow
access
numerous
are
unavailable
traditional
processes
will
advance
chemistry
proteins.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
63(3)
Published: Nov. 28, 2023
Abstract
Indole‐based
planar‐chiral
macrocycles
are
widely
found
in
natural
products
and
bioactive
molecules.
However,
sharp
contrast
to
the
preparation
of
indole‐based
axially
chiral
structures,
enantioselective
catalysis
is
still
a
formidable
task
so
far.
Here
we
report
an
N
‐heterocyclic
carbene
(NHC)‐catalyzed
intramolecular
atroposelective
macrocyclization
3‐carboxaldehyde
indole/pyrroles,
featuring
with
broad
substrate
scope
good
functional
group
tolerance,
allowing
for
rapid
access
diverse
indole/pyrrole‐based
various
tether‐lengths
(10–16
members)
yields
excellent
enantioselectivities.
Importantly,
macrocyclic
structures
both
planar
axial
chirality
were
directly
efficiently
obtained
through
this
protocol
enantioselectivities
diastereoselectivities.
In
addition,
these
synthesized
offer
many
possibilities
chemists
develop
new
catalysts
or
ligands,
as
well
reactions.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(25), P. 5323 - 5328
Published: June 17, 2024
Amino
acids
and
aromatic
nitrogen
heterocycles
are
widely
used
in
pharmaceuticals.
Herein,
we
present
an
effective
visible-light-driven
thiobenzoic
acid
(TBA)-catalyzed
decyanative
C(sp3)–H
heteroarylation
of
glycine
derivatives.
This
process
occurs
under
mild
straightforward
conditions,
affording
a
range
valuable
yet
challenging-to-obtain
α-heteroaryl
amino
Moreover,
this
organocatalytic
C(sp3)–C(sp2)
bond
formation
reaction
is
applicable
to
the
late-stage
modification
various
short
peptides.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(52)
Published: Nov. 11, 2023
A
disulfide
click
strategy
is
disclosed
for
stapling
to
enhance
the
metabolic
stability
and
cellular
permeability
of
therapeutic
peptides.
17-membered
library
reagents
with
adjustable
lengths
angles
was
established
rapid
double/triple
reactions,
bridging
S-terminal
peptides
from
3
18
amino
acid
residues
provide
18-
48-membered
macrocyclic
under
biocompatible
conditions.
The
constrained
exhibited
enhanced
anti-HCT-116
activity
a
locked
α-helical
conformation
(IC
Chemical Communications,
Journal Year:
2024,
Volume and Issue:
60(75), P. 10378 - 10381
Published: Jan. 1, 2024
Here
we
report
a
visible-light
facilitated
radical
addition
strategy
for
the
preparation
of
various
natural
or
unnatural
α-amino
acids
from
readily
available
glycine
derivatives
and
alkenes.
A
key
aspect
in
achieving
this
side
carbon
chain
introduction
reaction,
while
circumventing
well-documented
cyclization
pathway,
was
employment
radical-polar
crossover
under
redox
neutral
conditions.
Chemical Society Reviews,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 1, 2024
Owing
to
their
special
spatial
structures,
peptide-based
macrocycles
have
recently
shown
tremendous
promise
in
multidisciplinary
research
ranging
from
potent
antibiotics
against
resistant
strains
functional
biomaterials
with
novel
properties.
