Phosphine-promoted Thiol-Specific Bioconjugation with Allylic Acetates
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 24, 2025
Abstract
Thiol-specific
modification
of
proteins
through
conjugation
with
small
molecules
represents
a
critical
advancement
in
biological
research
and
therapeutic
development,
particularly
the
context
antibody-drug
conjugates
(ADCs)
for
targeted
cancer
therapy.
Despite
widespread
use
maleimide-based
linkers,
their
stability
under
physiological
conditions
remains
major
limitation,
often
compromising
efficacy.
In
this
investigation,
we
developed
novel
efficient
thiol-specific
bioconjugation
strategy
that
employs
allylic
acetate,
activated
by
recyclable
solid
phosphine
catalyst.
This
approach
achieves
high
yields
demonstrates
robust
bio-compatible,
room-temperature
conditions.
Notably,
it
sets
new
record
fastest
cysteine-conjugation
reaction
rate
reported
to
date,
constant
k2
=
1.49
×
10
6
M
−
1s
−
1.
The
method
expands
substrate
scope
introduces
sustainable,
environmentally
friendly
ADC
linker
design,
offering
significant
creation
stable,
biocompatible,
therapeutically
effective
compounds.
Язык: Английский
Electro-induced C-H/S-H Cross-Coupling for the Functionalization/Macrocyclization of Cysteine-Containing Peptides
Опубликована: Апрель 7, 2025
Abstract
The
electrochemical
platform
that
underpins
the
promising
future
of
selective
modifications
peptides
and
proteins,
however,
is
still
rather
underdeveloped.
Here
in,
an
electro-induced
umpolung
approach
enables
efficient
functionalization/macrocyclization
cysteine-containing
reported.
Notably,
this
method
utilizes
simple
halogen
source
takes
metal-mediated
atom
transfer
as
main
pathway
to
enable
in-situ
polarity
reversal,
highlighting
unique
possibilities
associated
with
activation
methods.
Under
mild
conditions,
cysteine
residue
can
be
well-labelled
high
chemo-selectivity
excellent
conversion.
This
transformation
tolerate
a
wide
range
valuable
enamines,
azoles,
partners,
also
utilized
macrocyclization
tactic
for
cyclic
peptide
synthesis
other
areas.
Язык: Английский
Sulfa-Michael Addition on Dehydroalanine: A Versatile Reaction for Protein Modifications
Organic Letters,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 23, 2024
Chemical
modification
of
proteins
has
been
widely
applied
in
diagnostic
and
therapeutic
processes.
Here,
we
report
a
novel
bioconjugation
between
sulfinic
acids
amino
acid
dehydroalanine
(Dha)
the
context
both
small
molecules
proteins.
This
conjugation
enables
rapid
formation
sulfone
linkages
chemoselective
disulfide-compatible
manner
under
biocompatible
conditions
with
Dha
residues
chemically
installed
thus
provides
robust
tool
that
is
simple
exquisite
site
selectivity
for
protein
functionalization
wide
range.
Язык: Английский
Efficient Approach to AviCys Analogues via Regio- and Stereoselective Hydrosulfuration of Ynamides
Organic Chemistry Frontiers,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
A
novel
synthetic
strategy
for
the
construction
of
AviCys
analogues
via
a
highly
efficient
regio-
and
stereoselective
hydrosulfuration
ynamides
was
reported.
Язык: Английский