Peptide Nanotubes Hamley, Ian W.
Angewandte Chemie (International ed.),
July 1, 2014, Volume:
53, Issue:
27
Journal Article
Peer reviewed
The self‐assembly of different classes of peptide, including cyclic peptides, amyloid peptides and surfactant‐like peptides into nanotube structures is reviewed. The modes of self‐assembly are ...discussed. Additionally, applications in bionanotechnology and synthetic materials science are summarized.
Building biotubes: The self‐assembly of peptide nanotubes from different classes of peptide, including cyclic peptides, amyloid peptides, and surfactant‐like peptides, is reviewed. Their applications in bionanotechnology and synthetic materials science are summarized.
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Protein interactions play a crucial role in a variety of biological processes. Therefore, regulation of these interactions has received considerable attention in terms of synthetic biology tool ...development. Of those, a toolbox of small peptides known as coiled coils (CCs) represents a unique effective tool for mediating protein-protein interactions because their binding specificity and affinity can be designed and controlled. CC peptides have been used as a building module for designing synthetic regulatory circuits in mammalian cells, construction of fast response to a signal, amplification of the response, and localization and regulation of function of diverse proteins. In this chapter, we describe a designed set of CCs used for mammalian cell engineering and provide a protocol for the construction of CC-mediated logic circuits in mammalian cells. Ultimately, these tools could be used for diverse biotechnological and therapeutic applications.
Membrane fusion results in the transport and mixing of (bio)molecules across otherwise impermeable barriers. In this communication, we describe the temporal control of targeted liposome–liposome ...membrane fusion and contents mixing using light as an external trigger. Our method relies on steric shielding and rapid, photoinduced deshielding of complementary fusogenic peptides tethered to opposing liposomal membranes. In an analogous approach, we were also able to demonstrate precise spatiotemporal control of liposome accumulation at cellular membranes in vitro.
Membrane fusion was temporally controlled by photolabile steric shielding of fusogenic liposomes. An analogous method also enabled spatiotemporal control of liposome accumulation at cellular membranes in vitro. This general approach represents a non‐invasive, user‐defined route towards vector‐based drug and gene delivery both in vitro and in vivo.
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Polymer-metal nanocomposites have widespread applications in biomedical fields such as imaging, catalysis, and drug delivery. These particles are characterized by combined organic and ...inorganic properties. Specifically, photothermal nanocomposites incorporating polymeric and plasmonic nanoparticles (NPs) have been designed for both triggered drug release and as imaging agents. However, the usual design of nanocomposites confers characteristic issues, among which are the decrease of optical properties and resulting low photothermal efficiency, as well as interactions with loaded drugs. Herein, we report the design of a core-satellite polymer-metal nanocomposite assembled by coiled-coil peptides and its superior photothermal efficiency compared to electrostatic-driven nanocomposites which is the standard design. We also found that the orientation of gold nanorods on the surface of polymeric NPs is of importance in the final photothermal efficiency and could be exploited for various applications. Our findings provide an alternative to current wrapping and electrostatic assembly of nanocomposites with the help of coiled-coil peptides and an improvement of the control over core-satellite assemblies with plasmonic NPs. It paves the way to highly versatile assemblies due to the nature of coiled-coil peptides to be easily modified and sensitive to pH or temperature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thermoresponsive resilin‐like polypeptides (RLPs) of various lengths were genetically fused to two different computationally designed coiled coil‐forming peptides with distinct thermal stability, to ...develop new strategies to assemble coiled coil peptides via temperature‐triggered phase separation of the RLP units. Their successful production in bacterial expression hosts was verified via gel electrophoresis, mass spectrometry, and amino acid analysis. Circular dichroism (CD) spectroscopy, ultraviolet‐visible (UV/Vis) turbidimetry, and dynamic light scattering (DLS) measurements confirmed the stability of the coiled coils and showed that the thermosensitive phase behavior of the RLPs was preserved in the genetically fused hybrid polypeptides. Cryogenic‐transmission electron microscopy and coarse‐grained modeling revealed that functionalizing the coiled coils with thermoresponsive RLPs leads to their thermally triggered noncovalent assembly into nanofibrillar assemblies.
Computationally designed coiled coil‐forming peptides were functionalized with thermoresponsive resilin‐like polypeptides (RLPs) of various lengths and produced via biosynthetic methods in bacterial expression hosts. Interactions between RLPs upon cooling below their upper critical solution temperature (UCST) resulted in nanofibrillar assembly.
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Patchy surfaces: An azide‐terminated self‐assembled monolayer was patterned with the peptide sequence (EIAALEK)3 by using microcontact printing. This sequence forms stable coiled‐coil heterodimers ...with the complementary peptide (KIAALKE)3. By introducing this peptide to the surface of phospholipid liposomes and cyclodextrin vesicles, liposomes and vesicles can be immobilized at the patterned surface.
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This review highlights a new paradigm in macromolecular nanomedicine – drug-free macromolecular therapeutics (DFMT). The effectiveness of the new system is based on biorecognition events without the ...participation of low molecular weight drugs. Apoptosis of cells can be initiated by the biorecognition of complementary peptide/oligonucleotide motifs at the cell surface resulting in the crosslinking of slowly internalizing receptors. B-cell CD20 receptors and Non-Hodgkin lymphoma (NHL) were chosen as the first target. Exposing cells to a conjugate of one motif with a targeting ligand decorates the cells with this motif. Further exposure of decorated cells to a macromolecule (synthetic polymer or human serum albumin) containing multiple copies of the complementary motif as grafts results in receptor crosslinking and apoptosis induction in vitro and in vivo. The review focuses on recent developments and explores the mechanism of action of DFMT. The altered molecular signaling pathways demonstrated the great potential of DFMT to overcome rituximab resistance resulting from either down-regulation of CD20 or endocytosis and trogocytosis of rituximab/CD20 complexes. The suitability of this approach for the treatment of blood borne cancers is confirmed. In addition, the widespread applicability of DFMT as a new concept in macromolecular therapeutics for numerous diseases is exposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The state-of-the art in water-soluble macromolecular therapeutics has been reviewed. First the design principles for polymer-drug conjugates are discussed followed by two recent developments in the ...field: a) The design, synthesis and properties of backbone degradable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates. The enhanced intravascular half-life of such conjugates creates a concentration gradient (blood vs. tumor) for an extended time interval resulting in increased solid tumor accumulation by enhanced permeability and retention (EPR) effect with concomitant increase in efficacy. b) Drug-free macromolecular therapeutics is a new paradigm in macromolecular therapeutics. Apoptosis in malignant cell is induced by crosslinking of cell surface non-internalizing receptors. Crosslinking of receptors is mediated by the biorecognition of two nanoconjugates containing high-fidelity complementary motifs (peptides or oligonucleotides). Results for the treatment of B cell lymphomas in animal models and patient cells demonstrate the high translational potential of this approach.
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Over the last four decades, significant efforts have been invested to develop vaccines against malaria. Although most efforts are focused on the development of
vaccines, the current availability of ...the parasite genomes, bioinformatics tools, and high throughput systems for both recombinant and synthetic antigen production have helped to accelerate vaccine development against the
parasite. We have previously
identified several
and
proteins containing α-helical coiled-coil motifs that represent novel putative antigens for vaccine development since they are highly immunogenic and have been associated with protection in many
functional assays. Here, we selected five pairs of
and
orthologous peptides to assess their sero-reactivity using plasma samples collected in
endemic African countries.
cross-reactivity was also investigated. The pairs
, and
resulted to be the most promising candidates for a cross-protective vaccine because they showed a high degree of recognition in direct and competition ELISA assays and cross-reactivity with their respective ortholog. The recognition of
peptides by plasma of
infected individuals indicates the existence of a high degree of cross-reactivity between these two
species. The design of longer polypeptides combining these epitopes will allow the assessment of their immunogenicity and protective efficacy in animal models.
Coiled‐coil peptides are frequently used to create new function upon the self‐assembly of supramolecular complexes. A multitude of coil peptide sequences provides control over the specificity and ...stability of coiled‐coil complexes. However, comparably little attention has been paid to the development of methods that allow the reversal of complex formation under non‐denaturing conditions. Herein, we present a reversible two‐state switching system. The process involves two peptide molecules for the formation of a size‐mismatched coiled‐coil duplex and a third, disruptor peptide that targets an overhanging end. A real‐time fluorescence assay revealed that the proximity between two chromophores can be switched on and off, repetitively if desired. Showcasing the advantages provided by non‐denaturing conditions, the method permitted control over the bivalent interactions of the tSH2 domain of Syk kinase with a phosphopeptide ligand.
Connect and disconnect: A reversible two‐state switching system was developed based on the formation of size‐mismatched and size‐matched coiled‐coil complexes. Interactions between three coiled‐coil peptides allow reversible switching of the optical properties and protein binding of peptide conjugates.
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