Expert Opinion on Drug Discovery,
Год журнала:
2022,
Номер
17(4), С. 413 - 422
Опубликована: Фев. 6, 2022
Introduction
Covalent
drugs
have
been
used
for
more
than
hundred
years,
but
gathered
larger
interest
in
the
last
two
decades.
There
are
currently
over
a
100
different
electrophilic
warheads
covalent
ligands,
and
there
several
considerations
tailoring
their
reactivity
against
target
of
interest,
which
is
still
challenging
task.Areas
covered
This
review
aims
to
give
an
overview
protein
labeling
chemical
biology
medicinal
chemistry.
The
discussed
by
targeted
residues,
mechanism
selectivity,
analyzed
through
three
datasets
including
our
collection
warheads,
CovPDB
database,
FDA
approved
drugs.
Moreover,
authors
summarize
general
practices
that
facilitate
selection
appropriate
warhead
interest.Expert
opinion
In
spite
numerous
only
fraction
them
current
drug
discovery
projects.
Recent
studies
identified
new
tractable
residues
applying
wider
array
chemistries.
However,
versatile,
selective
not
available
all
targetable
amino
acids,
hence
these
needed.
Broadening
toolbox
could
result
novel
inhibitors
even
targets
developing
with
significant
therapeutic
potential.
Chemical Reviews,
Год журнала:
2017,
Номер
117(12), С. 7762 - 7810
Опубликована: Май 10, 2017
Privileged
structures
have
been
widely
used
as
an
effective
template
in
medicinal
chemistry
for
drug
discovery.
Chalcone
is
a
common
simple
scaffold
found
many
naturally
occurring
compounds.
Many
chalcone
derivatives
also
prepared
due
to
their
convenient
synthesis.
These
natural
products
and
synthetic
compounds
shown
numerous
interesting
biological
activities
with
clinical
potentials
against
various
diseases.
This
review
aims
highlight
the
recent
evidence
of
privileged
chemistry.
Multiple
aspects
will
be
summarized
herein,
including
isolation
novel
derivatives,
development
new
methodologies,
evaluation
properties,
exploration
mechanisms
action
well
target
identification.
expected
comprehensive,
authoritative,
critical
community.
Angewandte Chemie International Edition,
Год журнала:
2017,
Номер
57(7), С. 1758 - 1784
Опубликована: Авг. 17, 2017
Hydrogen
isotopes
are
unique
tools
for
identifying
and
understanding
biological
chemical
processes.
isotope
labelling
allows
the
traceless
direct
incorporation
of
an
additional
mass
or
radioactive
tag
into
organic
molecule
with
almost
no
changes
in
its
structure,
physical
properties,
activity.
Using
deuterium-labelled
isotopologues
to
study
mass-spectrometric
patterns
generated
from
mixtures
biologically
relevant
molecules
drastically
simplifies
analysis.
Such
methods
now
providing
unprecedented
levels
insight
a
wide
continuously
growing
range
applications
life
sciences
beyond.
Tritium
(3
H),
particular,
has
seen
increase
utilization,
especially
pharmaceutical
drug
discovery.
The
efforts
costs
associated
synthesis
labelled
compounds
more
than
compensated
by
enhanced
molecular
sensitivity
during
analysis
high
reliability
data
obtained.
In
this
Review,
advances
application
hydrogen
described.
Chemical Reviews,
Год журнала:
2016,
Номер
116(24), С. 15284 - 15398
Опубликована: Дек. 16, 2016
The
widespread
applications
of
benzophenone
(BP)
photochemistry
in
biological
chemistry,
bioorganic
and
material
science
have
been
prominent
both
academic
industrial
research.
BP
photophores
unique
photochemical
properties:
upon
n−π*
excitation
at
365
nm,
a
biradicaloid
triplet
state
is
formed
reversibly,
which
can
abstract
hydrogen
atom
from
accessible
C–H
bonds;
the
radicals
subsequently
recombine,
creating
stable
covalent
C–C
bond.
This
light-directed
attachment
process
exploited
many
different
ways:
(i)
binding/contact
site
mapping
ligand
(or
protein)–protein
interactions;
(ii)
identification
molecular
targets
interactome
mapping;
(iii)
proteome
profiling;
(iv)
bioconjugation
site-directed
modification
biopolymers;
(v)
surface
grafting
immobilization.
also
has
practical
advantages,
including
low
reactivity
toward
water,
stability
ambient
light,
convenient
nm.
In
addition,
several
BP-containing
building
blocks
reagents
are
commercially
available.
this
review,
we
explore
"forbidden"
(transitions)
excitation-activated
world
photoinduced
by
touring
colorful
palette
recent
examples.
exploration,
will
see
pros
cons
using
photophores,
hope
that
novice
expert
photolabelers
enjoy
be
inspired
breadth
depth
possibilities.
Chemical Reviews,
Год журнала:
2018,
Номер
118(16), С. 7702 - 7743
Опубликована: Июль 24, 2018
The
conjugation
of
biomolecules
can
impart
materials
with
the
bioactivity
necessary
to
modulate
specific
cell
behaviors.
While
biological
roles
particular
polypeptide,
oligonucleotide,
and
glycan
structures
have
been
extensively
reviewed,
along
influence
attachment
on
material
structure
function,
key
role
played
by
strategy
in
determining
activity
is
often
overlooked.
In
this
review,
we
focus
chemistry
biomolecule
provide
a
comprehensive
overview
strategies
for
achieving
controlled
biomaterial
functionalization.
No
universal
method
exists
optimal
attachment,
here
will
discuss
both
relative
advantages
disadvantages
each
technique.
doing
so,
highlight
importance
carefully
considering
impact
suitability
technique
during
design.
Chemistry - A European Journal,
Год журнала:
2018,
Номер
25(1), С. 26 - 42
Опубликована: Июль 31, 2018
Abstract
In
the
last
decade,
visible‐light
photoredox
catalysis
has
emerged
as
a
powerful
strategy
to
enable
novel
transformations
in
organic
synthesis.
Owing
mild
reaction
conditions
(i.e.,
room
temperature,
use
of
visible
light)
and
high
functional‐group
tolerance,
could
represent
an
ideal
for
chemoselective
biomolecule
modification.
Indeed,
recent
trend
is
its
application
development
methodologies
amino
acid
Herein,
up‐to‐date
overview
photocatalytic
modification
single
acids,
peptides,
proteins
provided.
The
advantages
offered
by
suitability
biocompatible
are
described.
addition,
brief
consideration
current
limitations
approaches,
well
future
challenges
be
addressed,
discussed.
Signal Transduction and Targeted Therapy,
Год журнала:
2020,
Номер
5(1)
Опубликована: Май 21, 2020
Abstract
Natural
products
are
an
important
source
of
new
drugs
for
the
treatment
various
diseases.
However,
developing
natural
product-based
medicines
through
random
moiety
modification
is
a
lengthy
and
costly
process,
due
in
part
to
difficulties
associated
with
comprehensively
understanding
mechanism
action
side
effects.
Identifying
protein
targets
effective
strategy,
but
most
interact
multiple
targets,
which
complicate
this
process.
In
recent
years,
increasing
number
researchers
have
begun
screen
target
proteins
chemical
proteomics
approaches,
can
provide
more
comprehensive
array
active
small
molecules
unbiased
manner.
Typically,
experiments
identification
consist
two
key
steps:
(1)
probe
design
synthesis
(2)
fishing
identification.
decades,
five
different
types
proteomic
probes
their
respective
methods
been
developed
structures,
variety
approaches
invented.
Presently,
we
will
classify
these
application
scopes
characteristics
probes,
methods,
advantages
disadvantages
strategies.