This
review
provides
an
account
of
the
tryptophan-specific
conjugation
peptides
and
proteins
its
extensive
application
in
imaging
living
cells,
radiolabelling
proteins,
protein
engineering,
etc
.
Life Metabolism,
Journal Year:
2025,
Volume and Issue:
4(2)
Published: Feb. 7, 2025
Intestinal
farnesoid
X
receptor
(FXR)
antagonists
have
been
proven
to
be
efficacious
in
ameliorating
metabolic
diseases,
particularly
for
the
treatment
of
dysfunction-associated
steatohepatitis
(MASH).
All
reported
FXR
target
ligand-binding
pocket
(LBP)
receptor,
whereas
antagonist
acting
on
non-LBP
site
nuclear
(NR)
is
conceived
as
a
promising
strategy
discover
novel
antagonist.
Here,
we
postulated
hypothesis
antagonizing
by
disrupting
interaction
between
and
coactivators,
successfully
developed
series
macrocyclic
peptides
based
this
premise.
The
cyclopeptide
DC646
not
only
exhibits
potent
inhibitory
activity
FXR,
but
also
demonstrates
high
degree
selectivity
towards
other
NRs.
Moreover,
has
potential
therapeutic
benefit
MASH
an
intestinal
FXR-dependent
manner,
along
with
commendable
safety
profile.
Mechanistically,
distinct
from
known
antagonists,
specifically
binds
coactivator
binding
which
can
block
recruitment,
reducing
circulation
intestine-derived
ceramides
liver,
promoting
release
glucagon-like
peptide-1
(GLP-1).
Overall,
identify
that
targets
FXR-coactivator
interaction,
paving
way
new
approach
treating
antagonists.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 11, 2025
Here,
we
report
on
methods
for
late-stage
peptide
diversification
through
palladium-catalyzed
site-selective
C(sp2)–H
amination
of
tryptophan
residues
at
the
C4
position,
utilizing
tryptophan-amine
cross-links.
Our
strategy
enables
practical
access
to
C–N
bonds,
facilitating
construction
cyclopeptides
via
cyclodimerization
structurally
complex
peptides,
which
poses
significant
challenges
organic
synthesis.
The
synthetic
utility
this
protocol
is
demonstrated
synthesis
30-
38-membered
macrocyclic
peptides.
Chemistry - An Asian Journal,
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 24, 2024
Abstract
Macrocycles
are
essential
in
protein‐protein
interactions
and
the
preferential
intake
of
bioactive
scaffolds.
commonly
synthesized
by
late‐stage
macrolactonizations,
macrolactamizations,
transition
metal‐catalyzed
ring‐closing
metathesis,
S−S
bond‐forming
reactions,
copper‐catalyzed
alkyne–azide
cycloaddition.
Recently,
C−H
activation
strategies
have
gained
significant
interest
among
chemists
to
synthesize
macrocycles.
This
article
provides
a
comprehensive
overview
macrocyclization
via
bond
functionalization
heterocycle‐containing
peptides,
annulations,
heterocycle‐ring
construction
through
direct
functionalization.
In
first
part,
palladium
salt
catalyzed
coupling
with
indolyl
C(sp
3
)−H
2
bonds
for
is
reported.
The
second
part
summarizes
rhodium‐catalyzed
macrocyclizations
site‐selective
Earth‐abundant,
less
toxic
3d
metal
Mn‐catalyzed
cyclizations
reported
latter
part.
summary
expected
spark
emerging
methods
macrocycle
production
organic
synthesis
chemical
biology
practitioners,
helping
develop
discipline.
We
hope
that
this
mini‐review
will
also
inspire
synthetic
explore
new
broadly
applicable
C−C
intramolecular
activation.
Asian Journal of Organic Chemistry,
Journal Year:
2023,
Volume and Issue:
12(12)
Published: Nov. 10, 2023
Abstract
Pivaloyl‐directed
Rh(III)‐catalyzed
regioselective
C7
Ar
‐H
functionalization
of
protected
tryptophans
were
accomplished
with
1,4‐benzoquinones,
furnishing
a
series
quinone‐appended
tryptophan‐based
unnatural
amino
acids
in
high
yields.
Further,
the
late
stage
on
tryptophan‐containing
dipeptides
was
achieved
1,4‐benzoquinones
moderate
reactivity.
Abstract
A
ruthenium(II)‐catalyzed
C−H
acylmethylation
of
Trp‐containing
peptides
with
α
‐chloro
ketones
is
reported
here.
This
reaction
features
good
C‐2
selectivity
and
chemoselectivity,
making
it
suitable
for
late‐stage
modification
peptides.
Low‐cost
metal
ruthenium
as
a
catalyst
enables
the
to
be
conducted
on
gram
scale.
report
also
discusses
synthetic
applications
presents
method
remove
pyridine
directing
group.
In
addition,
plausible
mechanism
C(2)−H
proposed
in
this
article.
