ChemMedChem,
Journal Year:
2023,
Volume and Issue:
18(23)
Published: Oct. 11, 2023
Converting
known
ligands
into
photoswitchable
derivatives
offers
the
opportunity
to
modulate
compound
structure
with
light
and
hence,
biological
activity.
In
doing
so,
these
probes
provide
unique
control
when
evaluating
G-protein-coupled
receptor
(GPCR)
mechanism
function.
Further
conversion
of
such
compounds
covalent
probes,
as
tethered
(PTLs),
additional
advantages.
These
include
localization
PTLs
binding
pocket.
Covalent
increases
local
ligand
concentration,
improves
site
selectivity
may
improve
differences
between
respective
isomers.
This
work
describes
chemical,
photophysical
biochemical
characterizations
a
variety
designed
target
μ-opioid
(μOR).
were
modeled
on
fentanyl,
lead
disulfide-containing
agonist
found
covalently
interact
cysteine-enriched
mutant
this
medically-relevant
receptor.
Neuron,
Journal Year:
2023,
Volume and Issue:
111(24), P. 3926 - 3940.e10
Published: Oct. 16, 2023
Traditional
methods
for
site-specific
drug
delivery
in
the
brain
are
slow,
invasive,
and
difficult
to
interface
with
recordings
of
neural
activity.
Here,
we
demonstrate
feasibility
experimental
advantages
vivo
photopharmacology
using
"caged"
opioid
drugs
that
activated
light
after
systemic
administration
an
inactive
form.
To
enable
bidirectional
manipulations
endogenous
receptors
vivo,
developed
photoactivatable
oxymorphone
(PhOX)
naloxone
(PhNX),
variants
mu
receptor
agonist
antagonist
naloxone.
Photoactivation
PhOX
multiple
areas
produced
local
changes
occupancy,
metabolic
activity,
neuronal
calcium
neurochemical
signaling,
pain-
reward-related
behaviors.
Combining
photoactivation
optical
recording
extracellular
dopamine
revealed
adaptations
sensitivity
mesolimbic
circuitry
response
chronic
morphine
administration.
This
work
establishes
a
general
framework
study
basis
action.
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
61(18)
Published: Jan. 6, 2022
Serotonin
receptors
play
central
roles
in
neuromodulation
and
are
critical
drug
targets
for
psychiatric
disorders.
Optical
control
of
serotonin
receptor
subtypes
has
the
potential
to
greatly
enhance
our
understanding
spatiotemporal
dynamics
function.
While
other
neuromodulatory
have
been
successfully
rendered
photoswitchable,
reversible
photocontrol
not
achieved,
representing
a
major
gap
GPCR
photopharmacology.
Herein,
we
develop
first
tools
that
allow
such
control.
Azo5HT-2
shows
light-dependent
5-HT2A
R
agonism,
with
greater
activity
cis-form.
Based
on
docking
test
compound
analysis,
also
photoswitchable
orthogonal,
remotely-tethered
ligands
(PORTLs).
These
BG-Azo5HTs
provide
rapid,
reversible,
repeatable
optical
following
conjugation
SNAP-tagged
R.
Overall,
this
study
provides
foundation
broad
extension
photopharmacology
family.
Current Opinion in Pharmacology,
Journal Year:
2022,
Volume and Issue:
63, P. 102192 - 102192
Published: March 4, 2022
The
field
of
photopharmacology
Class
A
GPCR
ligands
has
recently
attracted
attention.
In
this
review
we
analyze
31
papers
on
currently
available
photoswitchable
for
GPCRs.
Using
the
six
most
recurring
terms
all
combined
paper
abstracts,
one
can
extract
overarching
goal
area
research:
"Photoswitchable
control
receptor
activity
with
light"
(represented
in
TOC
graphic).
We
design,
photochemistry
and
pharmacology
ligands.
Trends,
challenges
limitations
will
be
discussed.
number
efficient
that
allow
optical
modulation
function
various
vitro
assays
are
presented.
Moreover,
vivo
is
within
reach
first
reports
to
end
highlighted.
Chemical Reviews,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 25, 2025
Cell-surface
receptors
are
vital
for
controlling
numerous
cellular
processes
with
their
dysregulation
being
linked
to
disease
states.
Therefore,
it
is
necessary
develop
tools
study
and
the
signaling
pathways
they
control.
This
Review
broadly
describes
molecular
approaches
that
enable
1)
visualization
of
determine
localization
distribution;
2)
sensing
receptor
activation
permanent
readouts
as
well
in
real
time;
3)
perturbing
activity
mimicking
receptor-controlled
learn
more
about
these
processes.
Together,
have
provided
valuable
insight
into
fundamental
biology
helped
characterize
therapeutics
target
receptors.
Medicinal Research Reviews,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 6, 2025
The
use
of
photoswitchable
ligand
to
control
the
protein
functionalities
and
related
downstream
effects
in
an
on-off
manner
is
active
research
area
photopharmacology
medicinal
chemistry.
Temporal
grants
a
privilege
identify
crucial
role
particular
receptor
biological
occurrences
without
destroying
permanently.
Additionally,
light
can
be
applied
site-selectively
regulate
functionality
with
cellular
sub-cellular
levels
spatial
resolutions.
spatiotemporal
resolution
enables
probing
specific
receptor,
isoform,
or
signalling
pathway.
This
reversible
fast
highly
beneficial
studying
dynamic
processes,
including
but
not
limited
signal
transduction,
neurotransmission,
cell
divisions,
immune
response,
folding,
degradation.
Though
several
light-active
ligands
have
been
developed
efficiently,
only
few
reports
on
exist
literature.
Major
challenges
achieve
efficient
photoswitches
study
are
synthesis
strategy,
photostability
ligand,
bidirectional
visible
switching
ability
most
importantly
precise
controlling
local
concentration
desired
photoisomer
using
light.
site-specific
localization
depends
multiple
factors
like
nature
photoswitch,
binding
affinity
both
photoisomers,
molecular
diffusion
irradiation
conditions.
present
review
discusses
suitable
techniques
different
achieving
subcellular
dimension
functionality.
Multiple
strategies
discussed,
along
their
advantages
limitations,
explore
enormous
potentiality
these
approaches
manipulating
