Surface self-assembly of N-fluorenyl-9-methoxycarbonyl diphenylalanine on silica wafer

N-Fluorenyl-9-methoxycarbonyl diphenylalanine (Fmoc-FF-OH) was chemically immobilized to the surface of silica wafer as the "seed". When immersing this peptide attached silica wafer into the dipeptide aqueous solution, the occurrence of a pH triggered surface self-assembly resulted in the formation of peptide nanorods on the surface of silica wafer. This surface self-assembly exhibited a dependence on the concentration of the dipeptide aqueous solution. It was proposed that the self-assembly of this dipeptide on the surface of silica wafer was similar to that in aqueous solution. In comparison with the conventional physical adsorption on the substrates, the chemically attached self-assembled nanorods exhibited much improved adsorption capacity on the substrate surface.     

Rational design of a nanoscale helical scaffold derived from self-assembly of a dimeric coiled coil motif

We describe a model for the design of synthetic α-helical peptides that are competent for self-assembly into structurally defined supramolecular fibrils on the basis of architectural features that have been programmed into the peptide sequence. In order to test the validity of this experimental model, we have synthesized an oligopeptide YZ1 that was designed to conform to this model and to self-assemble into an α-helical fibril in which the structural sub-units that comprise the fibril corresponded to coiled coil dimers. Peptide YZ1 was prepared via conventional solid-phase peptide synthesis and was composed of 42 amino acid residues such that the sequence defined six distinct heptad repeats of a coiled coil structure. The sequence of YZ1 was designed to adopt an α-helical conformation in which the helical protomers self-associate in a parallel orientation with a staggered orientation between adjacent peptides that corresponded to an axial displacement of three heptads. The self-assembly of peptide YZ1 was examined at varying levels of structural hierarchy for compliance of the observed structures with the experimental model. Circular dichroism spectroscopy provided evidence for an α-helical coiled coil structure for YZ1 in aqueous solution, which could be reversibly denatured through thermal methods. TEM measurements indicated the formation of long aspect-ratio fibers of uniform diameter from aqueous solutions of YZ1, however the dimensions of the fibers suggested that lateral association occurred between the fibrils corresponding to the 2-stranded helical bundles. The α-helical coiled coil structure was confirmed in the solid-state for fibers derived from self-assembly of YZ1 by a combination of wide-angle X-ray diffraction and ¹³C CP/MAS NMR spectroscopy. SANS and synchrotron SAXS measurements on dilute aqueous solutions of YZ1 provided a fibril diameter that corresponded to the lateral dimensions estimated for a dimeric coiled coil assembly on the basis of structural determinations of model peptides.     

Mixed-phase synthesis of glycopeptides using a N-peptidyl-2,4-dinitrobenzenesulfonamide-thioacid ligation strategy

A strategy for the solid phase peptide synthesis (SPPS) and coupling of N-peptidyl and N-glycopeptidyl 2,4-dinitrobenzenesulfonamides (dNBS) with C-terminal peptidyl thioacids has been developed. The resulting N-dDNBS peptides were coupled to generate longer peptides. Ligation reactions were complete within 15 to 20 min.     

Anion-directed self-assembly of a 2,6-bis(2-anilinoethynyl)pyridine bis(amide) scaffold

Bis(sulfonamide) receptors based on the 2,6-bis(2-anilinoethynyl)pyridine scaffold form persistent dimers with water and halides in solution and in the solid-state. The structurally related bis(amide) receptor derived from 3,5-dinitrobenzoyl chloride is a dimer in the solid-state with two HCl molecules directing the self-assembly. The 2+2 dimer, with a twisted ‘S’-shaped backbone, is held together by six hydrogen bonds. Dissolution of the (H2⁺√Cl ^? )₂ adduct in CHCl₃ results, however, in a monomeric structure. DOSY and ¹H NMR experiments were used to identify the dominance of monomer in solution for both 2 and H2⁺√Cl ^? . The ‘OFF–ON’ fluorescence response of 2,6-bis(2-anilinoethynyl)pyridine is retained with amide arms.     

Electroaddressing agarose using Fmoc-phenylalanine as a temporary scaffold

Electroaddressing, the use of imposed electrical stimuli to guide assembly, is attractive because electrical stimuli can be conveniently applied with high spatial and temporal resolution. Several electroaddressing mechanisms have been reported in which electrode-induced pH gradients trigger stimuli-responsive materials to undergo localized sol-gel transitions to form hydrogel matrices. A common feature of existing hydrogel electrodeposition mechanisms is that the deposited matrix retains residual charged, acidic, or basic (macro)molecules. Here, we report that pH-responsive fluorenyl-9-methoxycarbonyl-phenylalanine (Fmoc-Phe) can be used to codeposit the neutral and thermally responsive polysaccharide agarose. Upon cooling, an agarose network is generated and Fmoc-Phe can be removed. The Fmoc-Phe-mediated codeposition of agarose is simple, rapid, spatially selective, and allows for the electroaddressing of a bioactive matrix.     

Thio-mediated synthesis of derivatized N-linked glycopeptides using isonitrile chemistry

The reaction of oligosaccharide isonitriles with peptide thioacids in the presence of bulky thiophenol as activator to provide N-linked glycopeptides at room temperature is described.     

Bioinspired vesicle restraint and mobilization using a biopolymer scaffold

Biology employs vesicles to package molecules (e.g., neurotransmitters) for their targeted delivery in response to specific spatiotemporal stimuli. Biology is also capable of employing localized stimuli to exert an additional control on vesicle trafficking; intact vesicles can be restrained (or mobilized) by association with (or release from) a cytoskeletal scaffold. We mimic these capabilities by tethering vesicles to a biopolymer scaffold that can undergo (i) stimuli-responsive network formation (for vesicle restraint) and (ii) enzyme-catalyzed network cleavage (for vesicle mobilization). Specifically, we use the aminopolysaccharide chitosan as our scaffold and graft a small number of hydrophobic moieties onto its backbone. These grafted hydrophobes can insert into the bilayer to tether vesicles to the scaffold. Under acidic conditions, the vesicles are not restrained by the hydrophobically modified chitosan (hm-chitosan) because this scaffold is soluble. Increasing the pH to neutral or basic conditions allows chitosan to form interpolymer associations that yield a strong, insoluble restraining network. Enzymatic hydrolysis of this scaffold by chitosanase cleaves the network and mobilizes intact vesicles. Potentially, this approach will provide a controllable means to store and liberate vesicle-based reagents/therapeutics for microfluidic/medical applications.     

Supramolecular helical porphyrin arrays using DNA as a scaffold

A diphenyl porphyrin substituted nucleotide was incorporated site specifically into DNA, leading to helical stacked porphyrin arrays in the major groove of the duplexes. The porphyrins show an electronic interaction which is significantly enhanced compared to the analogous tetraphenyl porphyrin (TPP) as shown in the large exciton coupling of the porphyrin B-band absorbance. Analogous to the TPP-DNA, an induced helical secondary structure is observed in the single strand porphyrin-DNA. The modified DNA can be hybridised to an immobilised complementary strand leading to fluorescent beads.     

Robust gels created using a self-assembly and covalent capture strategy

The self-assembly of dendritic building blocks containing multiple terminal alkenes on their surfaces yields soft gel-phase materials--subsequent Grubbs' metathesis leads to covalent cross-linking between the alkenes and the formation of robust swellable gels.     

Transparent electrodes fabricated via the self-assembly of silver nanowires using a bubble template

To shore up the demand of transparent electrodes for wide applications such as organic light emitting diodes and solar cells, transparent electrodes are required as an alternative for indium tin oxide electrodes. Herein the self-assembly method with a bubble template paves the way for cost-effective fabrication of transparent electrodes with high conductivity and transparency using self-assembly of silver nanowires (AgNWs) in a bubble template. AgNWs were first dispersed in water that was bubbled with a surfactant and a thickening agent. Furthermore, these AgNWs were assembled by lining along the bubble ridges. When the bubbles containing the AgNWs were sandwiched between two glass substrates, the bubble ridges including the AgNWs formed continuous polygonal structures. Mesh structures were formed on both glass substrates after air-drying. The mesh structures evolved into mesh transparent electrodes following heat-treatment. The AgNW mesh structure exhibited a low sheet resistance of 6.2 Ω/square with a transparency of 84% after heat treatment at 200 °C for 20 min. The performance is higher than that of transparent electrodes with random networks of AgNWs. Furthermore, the conductivity and transparency of the mesh transparent electrodes can be adjusted by changing the amount of the AgNW suspension and the space between the two glass substrates.     

Using the bending beam model to estimate the elasticity of diphenylalanine nanotubes

The core recognition motif of the amyloidogenic beta-amyloid polypeptide, diphenylalanine peptide, has previously been shown to self-assemble into discrete, well-ordered, stiff nanotubes under mild conditions. The nanotubes keep the same morphology from room temperature up to 100 degrees C. In the presented study, we applied the bending beam model to atomic force microscopy images of diphenylalanine nanotubes suspended across cavities and obtained the Young's modulus 27 +/- 4 GPa and the shear modulus 0.21 +/- 0.03 GPa. We also showed that the elasticity of these nanotubes is stable within the same temperature range and at relative humidity from 0% to 70%. This study furthers our understanding of the structure and properties of these nanotubes, which are important for their potential applications in biotechnology.     

Hierarchical assembly of diphenylalanine into dendritic nanoarchitectures

Highly ordered, multi-dimensional dendritic nanoarchitectures were created via self-assembly of diphenylalanine from an acidic buffer solution. The self-similarity of dendritic structures was characterized by examining their fractal dimensions with the box-counting method. The fractal dimension was determined to be 1.7, which demonstrates the fractal dimension of structures generated by diffusion limited aggregation on a two-dimensional substrate surface. By confining the dendritic assembly of diphenylalanine within PDMS microchannels, the self-similar dendritic growth could be hierarchically directed to create linearly assembled nanoarchitectures. Our approach offers a novel pathway for creating and directing hierarchical nanoarchitecture from biomolecular assembly.     

Direct observation of the release of phenylalanine from diphenylalanine nanotubes

The core recognition motif of the amyloidogenic beta-amyloid polypeptide is a dipeptide of phenylalanine. This dipeptide readily self-assembles to form discrete, hollow nanotubes with high persistence lengths. The simplicity of the nanotube formation, combined with ideal physical properties, make these nanotubes highly desirable for a range of applications in bionanotechnology. To fully realize the potential of such structures, it is first necessary to gain a comprehensive understanding of their chemical and physical properties. Previously, the thermal stability of these nanotubes has been investigated by electron microscopy. Here, we further our understanding of the structural stability of the nanotubes upon dry-heating using the atomic force microscope (AFM), and for the first time identify their degradation product utilizing time-of-flight secondary-ion mass spectrometry. We show that the nanotubes are stable at temperatures up to 100 degrees C, but on heating to higher temperatures begin to lose their structural integrity with an apparent collapse in tubular structure. With further increases in temperature up to and above 150 degrees C, there is a degradation of the structure of the nanotubes through the release of phenylalanine building blocks. The breakdown of structure is observed in samples that are either imaged at elevated temperatures or imaged following cooling, suggesting that once phenylalanine is lost from the nanotubes they are susceptible to mechanical deformation by the imaging AFM probe. This temperature-induced plasticity may provide novel properties for these peptide nanotubes, including possible applications as scaffolds and drug delivery devices.     

Improving SH3 domain ligand selectivity using a non-natural scaffold

BACKGROUND: Src homology 3 (SH3) domains bind sequences bearing the consensus motif PxxP (where P is proline and x is any amino acid), wherein domain specificity is mediated largely by sequences flanking the PxxP core. This specificity is limited, however, as most SH3 domains show high ligand cross-reactivity. We have recently shown that diverse N-substituted residues (peptoids) can replace the prolines in the PxxP motif, yielding a new source of ligand specificity. RESULTS: We have tested the effects of combining multiple peptoid substitutions with specific flanking sequences on ligand affinity and specificity. We show that by varying these different elements, a ligand can be selectively tuned to target a single SH3 domain in a test set. In addition, we show that by making multiple peptoid substitutions, high-affinity ligands can be generated that completely lack the canonical PxxP motif. The resulting ligands can potently disrupt natural SH3-mediated interactions. CONCLUSIONS: Peptide-peptoid hybrid scaffolds yield SH3 ligands with markedly improved domain selectivity, overcoming one of the principal challenges in designing inhibitors against these domains. These compounds represent important leads in the search for orthogonal inhibitors of SH3 domains, and can serve as tools for the dissection of complex signaling pathways.     

Combinatorial synthesis of natural product-like molecules using a first-generation spiroketal scaffold

Recently, significant attention has been focused on the synthesis small-molecule libraries based on natural product or natural product-like structures. In this paper, we report our initial studies on the use of the 1,7-dioxaspiro[5,5]undecane (spiroketal) moiety as a rigid-core template for elaboration using parallel synthesis techniques. The synthesis of a spiroketal scaffold that is reminiscent of the spiroketal subunits found in the spiroketal macrolide antibiotics will be described. Elaboration of three independently addressable functional groups on the scaffold using solution-phase parallel synthesis techniques led to the preparation of a small library of natural product-like compounds. These studies pave the way for evaluation of highly functionalized spiroketals in phenotypic assays and as prospective antagonists of protein-protein interactions.     

Synthesis of macrocyclic,potential protease inhibitors using a generic scaffold

A generic macrocyclic peptide structure 2 was designed as a potential inhibitor of a range of proteinases, by using as a basis for the design the known structures of a series of enzyme-inhibitor complexes. The macrocyclic nature of the target 2 was chosen so as to reduce the entropic advantage in the hydrolytic enzymatic step, and thereby to inhibit the function of the enzyme. The nature of the linking group was identified as a benzoxazole by molecular modeling, so as to preserve the recognized conformation of the peptide chain. The specificity of the potential inhibitor was tuned by variation of the P(1) group (by incorporating phenylalanine, aspartic acid, or lysine), to allow recognition by different enzyme classes. The targets were prepared from the bis-amino acid derivative 5, itself prepared using the Pd-catalyzed coupling of an organozinc reagent with the iodobenzothiazole 7 and subsequent macrocyclization of the open-chain derivatives 22-24 using HATU. None of the macrocylic compounds 25, 28-30, and 32 inhibited their target enzymes. NMR and MS studies on the interaction of macrocycle 29 and chymotrypsin established that compound 29 was in fact a substrate of the enzyme. This result indicated that while the design had been partially successful in identifying a compound that bound, the reduction in entropic advantage due to its macrocyclic nature was not sufficient to allow 29 to act as an inhibitor.     

Dynamic self-assembly of nanoparticles using thermotropic liquid crystals

ABSTRACT

3D nanoparticle-based materials with reconfigurable structure have gained vast attention due to the unique possibility of tailoring nanoparticle-related quantum confinement effects. These properties make active nanoparticle assemblies promising candidates for future optoelectronic and metamaterial technologies; however, integration of these materials into real-world applications is still challenging. In this context, the use of stimuli responsive liquid-crystals (LCs) offers a fascinating and industrially feasible strategy for active directing of NPs. Here, we briefly review LCs/NPs hybrid systems in which dynamic behaviour is achieved by affecting either LC matrix or LC ligands. We also experimentally evaluate a complementary strategy based on directly affecting metallic core of LC-covered NPs in an Ostwald ripening process.