6 research outputs found
Supramolecular Polymers Formed by ABC Miktoarm Star Peptides
We
report here the design and synthesis of an ABC miktoarm star peptide
connecting through a lysine junction a short peptide sequence and
two hydrophobic but immiscible blocks (a hydrocarbon and a fluorocarbon).
The designed molecule can self-assemble into one-dimensional nanostructures
with a great diversity of kinetically evolving morphologies in aqueous
solution, while molecules that contain only one of the two hydrophobic
blocks form structurally similar filaments. We believe the rich assembly
behavior and morphological evolution are a direct reflection of the
molecular frustration present within the filament core as a result
of the incompatibility of the fluorocarbon and hydrocarbon segments.
Our finding opens new opportunities for creating complex supramolecular
polymers through the architecture design of small molecular building
units
Rational Design of MMP Degradable Peptide-Based Supramolecular Filaments
One-dimensional nanostructures formed
by self-assembly of small
molecule peptides have been extensively explored for use as biomaterials
in various biomedical contexts. However, unlike individual peptides
that can be designed to be specifically degradable by enzymes/proteases
of interest, their self-assembled nanostructures, particularly those
rich in β-sheets, are generally resistant to enzymatic degradation
because the specific cleavage sites are often embedded inside the
nanostructures. We report here on the rational design of β-sheet
rich supramolecular filaments that can specifically dissociate into
less stable micellar assemblies and monomers upon treatment with matrix
metalloproteases-2 (MMP-2). Through linkage of an oligoproline segment
to an amyloid-derived peptide sequence, we first synthesized an amphiphilic
peptide that can undergo a rapid morphological transition in response
to pH variations. We then used MMP-2 specific peptide substrates as
multivalent cross-linkers to covalently fix the amyloid-like filaments
in the self-assembled state at pH 4.5. Our results show that the cross-linked
filaments are stable at pH 7.5 but gradually break down into much
shorter filaments upon cleavage of the peptidic cross-linkers by MMP-2.
We believe that the reported work presents a new design platform for
the creation of amyloid-like supramolecular filaments responsive to
enzymatic degradation
Dataset: Linking deep-time subduction history to modern day expressions of dynamic topography
Supplemental files for the submitted manuscript "Linking deep-time subduction history to modern day expressions of dynamic topography" by C. M. Calvelage, Jonny Wu, Lorenzo Colli, Yi-An Lin, and Yingcai ZhengGlobal predicted dynamic topography files for each spherical harmonic degree 3, 10, and 40. Columns are longitude, latitude, and predicted dynamic topography (positive values=uplift; negative=subsidence).GPlates digital plate reconstruction files for the Earthbyte (Matthews et al., 2016) and Tomopac (Wu et al., 2022) plate reconstructions.For inquiries regarding the contents of this dataset, please contact the Corresponding Author listed in the README.txt file. Administrative inquiries (e.g., removal requests, trouble downloading, etc.) can be directed to [email protected]</p
One-Step Fabrication of Self-Assembled Peptide Thin Films with Highly Dispersed Noble Metal Nanoparticles
Fabrication of organic thin films
with highly dispersed inorganic
nanoparticles is a very challenging topic. In this work, a new approach
that combines electron-induced molecular self-assembly with simultaneous
nanoparticle formation by room temperature electron reduction was
developed to prepare peptide thin films with highly dispersed noble
metal nanoparticles. Argon glow discharge was employed as the resource
of electrons. The peptide motif KLVFF (Aβ<sub>16–20</sub>) self-assembled into two-dimensional membranes under the influence
of hydrated electrons, while the metal ions in solution can be simultaneously
reduced by electrons to form nanoparticles. Our TEM imaging reveals
that metal nanoparticles were well-distributed in the resulting peptide
thin films. Our results also suggest that the size of metal nanoparticles
can be tuned by varying the initial concentration of the metal ion.
This simple approach can be viewed as a promising strategy to create
hybrid thin films that integrate functional inorganics into biomolecule
scaffolds
A Hybrid Protein–Polymer Nanoworm Potentiates Apoptosis Better than a Monoclonal Antibody
B-cell lymphomas continue to occur with a high incidence. The chimeric antibody known as Rituximab (Rituxan) has become a vital therapy for these patients. Rituximab induces cell death <i>via</i> binding and clustering of the CD20 receptor by Fcγ expressing effector cells. Because of the limited mobility of effector cells, it may be advantageous to cluster CD20 directly using multivalent nanostructures. To explore this strategy, this manuscript introduces a nanoparticle that assembles from a fusion between a single chain antibody and a soluble protein polymer. These hybrid proteins express in <i>Escherichia coli</i> and do not require bioconjugation between the antibody and a substrate. Surprisingly a fusion between an anti-CD20 single chain antibody and a soluble protein polymer assemble worm-like nanostructures, which were characterized using light scattering and cryogenic transmission electron microscopy. These nanoworms competitively bind CD20 on two B-cell lymphoma cell lines, exhibit concentration-dependent induction of apoptosis, and induce apoptosis better than Rituximab alone. Similar activity was observed <i>in vivo</i> using a non-Hodgkin lymphoma xenograft model. In comparison to Rituximab, systemic nanoworms significantly slowed tumor growth. These findings suggest that hybrid nanoworms targeted at CD20 may be useful treatments for B-cell related malignancies. Because of the ubiquity of antibody therapeutics, related nanoworms may have uses against other molecular targets
Bifunctional Elastin-like Polypeptide Nanoparticles Bind Rapamycin and Integrins and Suppress Tumor Growth in Vivo
Recombinant
protein–polymer scaffolds such as elastin-like
polypeptides (ELPs) offer drug-delivery opportunities including biocompatibility,
monodispersity, and multifunctionality. We recently reported that
the fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle
(FSI) increases rapamycin (Rapa) solubility, suppresses tumor growth
in breast cancer xenografts, and reduces side effects observed with
free-drug controls. This new report significantly advances this carrier
strategy by demonstrating the coassembly of two different ELP diblock
copolymers containing drug-loading and tumor-targeting domains. A
new ELP nanoparticle (ISR) was synthesized that includes the canonical
integrin-targeting ligand (Arg-Gly-Asp, RGD). FSI and ISR mixed in
a 1:1 molar ratio coassemble into bifunctional nanoparticles containing
both the FKBP domain for Rapa loading and the RGD ligand for integrin
binding. Coassembled nanoparticles were evaluated for bifunctionality
by performing in vitro cell-binding and drug-retention assays and
in vivo MDA-MB-468 breast tumor regression and tumor-accumulation
studies. The bifunctional nanoparticle demonstrated superior cell
target binding and similar drug retention to FSI; however, it enhanced
the formulation potency, such that tumor growth was suppressed at
a 3-fold lower dose compared to an untargeted FSI–Rapa control.
This data suggests that ELP-mediated scaffolds are useful tools for
generating multifunctional nanomedicines with potential activity in
cancer