A Collagen Triple Helix without the Superhelical Twist
ACS Central Science,
Journal Year:
2025,
Volume and Issue:
11(2), P. 331 - 345
Published: Feb. 4, 2025
Collagens
are
ubiquitous
in
biology:
functioning
as
the
backbone
of
extracellular
matrix,
forming
primary
structural
components
key
immune
system
complexes,
and
fulfilling
numerous
other
roles
a
variety
systems.
Despite
this,
there
is
limited
understanding
how
triple
helices,
basic
collagen
units,
pack
into
collagenous
assemblies.
Here
we
use
peptide
self-assembly
to
design
assemblies
based
on
C1q
collagen-like
region.
Using
cryo-EM
solved
structure
one
assembly
3.5
Å
resolution
built
an
atomic
model.
From
identify
helix
conformation
with
no
superhelical
twist,
starkly
contrast
canonical
right-handed
helix.
This
nontwisting
region
allows
for
unique
hydroxyproline
stacking
between
adjacent
helices
also
results
formation
exposed
cavity
rings
hydrophobic
amino
acids
packed
symmetrically.
We
find
precedent
such
arrangement
designed
substituted
various
locations
probe
stabilizing
acid
interactions
complex.
The
stability
these
altered
complexes
behaves
predicted
by
our
Our
findings,
combined
extremely
experimental
data
packing
literature,
suggest
that
may
adopt
far
more
varied
conformational
landscape
than
previously
appreciated.
hypothesize
this
particularly
likely
termini
at
discontinuities
required
Xaa-Yaa-Gly
repeating
sequence,
discontinuity
found
majority
class
proteins
many
collagen-associated
diseases.
Language: Английский
Supramolecular assembly of collagen mimetic peptide D-periodic fibrils and nanoassemblies
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 16, 2025
Abstract
The
collagen
triple
helix
assembles
hierarchically
into
bundled
oligomers,
solvated
networks
and
fibers.
Synthetic
peptide
assemblies,
driven
by
supramolecular
interactions,
can
form
single
helices
through
intrahelical
amino
acid
pairs,
but
the
principles
guiding
interhelical
associations
higher-order
structures
remain
unclear.
Here,
we
incorporate
cation-
π
electrostatic
charge
pairs
to
probe
interactions
elucidate
mechanisms
driving
assembly
fibrils,
nanotubes,
nanosheets.
Introducing
a
fibrillating
mimetic
resulted
in
D-periodic
fibrils
with
pH-sensitive
gelation.
Modifying
presentation
of
also
enabled
characterization
another
fibril
resembling
cartilage
collagens,
featuring
inner
outer
layers.
Enhancing
promoted
antiparallel
assembly,
leading
formation
nanotubes
packing
behavior
correlates
where
parallel
favor
formation,
drive
nanotube
nanosheet
assembly.
Language: Английский
Hierarchical Assemblies of Collagen-Mimetic Peptides: From a Fundamental Understanding to Developing Biomaterials
Langmuir,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 4, 2025
Collagen
is
the
most
abundant
protein
in
animals
and
crucial
for
maintaining
structural
functional
integrity
of
extracellular
matrix.
Its
primary
structure
consists
∼300
repeats
Xaa-Yaa-Gly
triplet,
where
Xaa
Yaa
are
often
proline
(Pro)
4-(R)-hydroxyproline
(Hyp)
residues,
respectively.
fundamentally
a
right-handed
triple
helix
that
undergoes
self-association,
forming
complex
supramolecular
structures
body.
Despite
extensive
study,
detailed
mechanisms
behind
its
higher-order
assembly
remain
unclear
due
to
challenges
purification
post-translational
modifications
it
undergoes.
To
better
understand
molecular
aspects
collagen's
structure,
researchers
developed
collagen-mimetic
peptides
(CMPs)─short
composed
7-17
triplets─easily
synthesized
laboratory.
Over
years,
research
on
CMPs
has
provided
significant
insights
into
formation
stability
collagen
helix.
However,
creating
multihierarchical
self-assembled
beyond
remains
challenging.
Recently,
various
strategies
such
as
covalent
linkages,
salt-bridge
interactions,
incorporation
hydrophobic
groups,
metal-coordinated
assembly,
coassembly
with
foreign
partners
have
been
employed
design
CMP
assemblies.
These
innovations
led
creation
fibers,
2D
sheets,
wires,
spherical
micelles.
This
progress
paved
way
rational
novel
peptide-based
biomaterials,
which
may
offer
advantages
over
animal-derived
collagen,
including
absence
potential
allergens
contaminants.
review
highlights
recent
advancements
design,
discussing
principles,
challenges,
prospects
these
biomaterials
clinical
applications.
Language: Английский
Balancing Chemical and Supramolecular Stability in OEGylated Supramolecular Polymers for Systemic Drug Delivery
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 15, 2025
The
chemical
conjugation
of
poly(ethylene
glycol)
(PEG)
to
therapeutic
agents,
known
as
PEGylation,
is
a
well-established
strategy
for
enhancing
drug
solubility,
stability,
and
pharmacokinetics.
Here,
we
report
on
class
supramolecular
polymeric
prodrugs
by
utilizing
oligo(ethylene
(OEG)
modify
the
hydrophobic
anticancer
camptothecin
(CPT).
These
OEGylated
prodrugs,
despite
their
low
molecular
weight,
spontaneously
self-assemble
into
polymers
(SPs)
with
tubular
morphology,
featuring
dense
OEG
coating
surface.
By
designing
biodegradable
linkers
varying
stabilities,
investigated
how
release
kinetics
CPT
influence
in
vitro
vivo
performance
these
SPs.
Our
findings
demonstrate
that
self-assembling
(SAPDs)
self-immolative
disulfanyl-ethyl
carbonate
(etcSS)
linker
exhibit
faster
rate
than
those
reducible
disulfanyl
butyrate
(buSS)
linker,
leading
higher
potency
significantly
improved
antitumor
efficacy.
Notably,
two
stable
SPs,
Tubustecan
(TT)
1E
TT
7E,
outperformed
irinotecan─a
clinically
approved
prodrug─in
colon
cancer
model,
achieving
enhanced
tumor
growth
inhibition
prolonged
animal
survival.
results
highlight
potential
OEGylation
an
important
engineering
drug-based
underscore
critical
role
stability
vs
optimizing
prodrug
design.
Language: Английский