ACS Bio & Med Chem Au,
Journal Year:
2024,
Volume and Issue:
5(1), P. 16 - 30
Published: Nov. 27, 2024
Cytochrome
P450
enzymes
catalyze
a
large
number
of
oxidative
transformations
that
are
responsible
for
natural
product
synthesis.
Recent
studies
have
revealed
their
unique
ability
to
the
formation
C-N
and
C-S
bonds,
broadening
biosynthetic
applications.
However,
enzymatic
mechanisms
behind
these
reactions
still
unclear.
This
review
focuses
on
theoretical
insights
into
P450-catalyzed
bond
formation.
The
key
roles
conformational
dynamics
substrate
radicals,
influenced
by
enzyme
environment,
in
modulating
selectivity
reactivity
highlighted.
Understanding
reaction
offers
valuable
guidance
engineering
design
The Journal of Physical Chemistry A,
Journal Year:
2024,
Volume and Issue:
128(34), P. 7167 - 7176
Published: Aug. 20, 2024
Compound
I
(Cpd
I)
plays
a
pivotal
role
in
substrate
transformations
within
the
catalytic
cycle
of
cytochrome
P450
enzymes
(P450s).
A
key
constituent
Cpd
is
iron(IV)-oxo
unit,
structural
motif
also
found
other
heme
and
nonheme
enzymes.
In
this
study,
we
performed
ab
initio
valence
bond
(VB)
calculations,
employing
self-consistent
field
(VBSCF)
breathing
orbital
(BOVB)
methods,
to
unveil
bonding
nature
vital
"Fe(IV)═O″
unit
bioinorganic
chemistry.
Comparisons
were
drawn
with
triplet
O
EJNMMI Radiopharmacy and Chemistry,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Jan. 2, 2024
Abstract
Background
Transglutaminase
2
(TGase
2)
is
a
multifunctional
protein
and
has
prominent
role
in
various
(patho)physiological
processes.
In
particular,
its
transamidase
activity,
which
rather
latent
under
physiological
conditions,
gains
importance
malignant
cells.
Thus,
there
great
need
of
theranostic
probes
for
targeting
tumor-associated
TGase
2,
targeted
covalent
inhibitors
appear
to
be
particularly
attractive
as
vector
molecules.
Such
an
inhibitor,
equipped
with
radionuclide
suitable
noninvasive
imaging,
would
supportive
answering
the
general
question
on
possibility
functional
characterization
2.
For
this
purpose,
recently
developed
18
F-labeled
N
ε
-acryloyllysine
piperazide
[
F]7b
,
potent
selective
irreversible
inhibitor
was
subject
detailed
radiopharmacological
herein.
Results
An
alternative
radiosynthesis
presented,
demands
less
than
300
µg
respective
trimethylammonio
precursor
per
synthesis
provides
good
radiochemical
yields
(17
±
7%)
high
(radio)chemical
purities
(≥
99%).
Ex
vivo
biodistribution
studies
healthy
mice
at
5
60
min
p.i.
revealed
no
permanent
enrichment
F-activity
tissues
exception
bone
tissue.
pretreatment
ketoconazole
vitro
murine
liver
microsome
complemented
by
mass
spectrometric
analysis
demonstrated
that
uptake
originates
from
metabolically
released
F]fluoride.
Further
metabolic
transformations
include
mono-hydroxylation
glucuronidation.
Based
blood
sampling
data
experiments,
pharmacokinetic
parameters
such
plasma
intrinsic
clearance
were
derived,
substantiated
apparently
rapid
distribution
elimination
organisms.
A
2-mediated
different
tumor
cell
lines
could
not
proven.
Moreover,
evaluation
melanoma
xenograft
models
based
A375-hS100A4
+)
MeWo
−)
cells
ex
PET
imaging
indicative
specific
targeting.
Conclusion
valuable
radiometric
tool
study
conditions.
However,
suitability
strongly
limited
due
unfavorable
properties
rodents.
Consequently,
perspective
requires
appropriate
structural
modifications
overcome
these
limitations.
ACS Bio & Med Chem Au,
Journal Year:
2024,
Volume and Issue:
5(1), P. 16 - 30
Published: Nov. 27, 2024
Cytochrome
P450
enzymes
catalyze
a
large
number
of
oxidative
transformations
that
are
responsible
for
natural
product
synthesis.
Recent
studies
have
revealed
their
unique
ability
to
the
formation
C-N
and
C-S
bonds,
broadening
biosynthetic
applications.
However,
enzymatic
mechanisms
behind
these
reactions
still
unclear.
This
review
focuses
on
theoretical
insights
into
P450-catalyzed
bond
formation.
The
key
roles
conformational
dynamics
substrate
radicals,
influenced
by
enzyme
environment,
in
modulating
selectivity
reactivity
highlighted.
Understanding
reaction
offers
valuable
guidance
engineering
design
