Self-Assembly of Hybrid Peptide−DNA Nanostructures using Homotrimeric Coiled-Coil/Nucleic Acid Building Blocks

Peptides and DNA are two of the most commonly used self-assembling biological molecules for the construction of nanomaterials. However, there are only a few examples that combine these two self-assembly motifs as key structural elements in a nanostructure. We report on the synthesis of a peptide−DNA conjugate that self-assembles into a stable homotrimer based on the coiled-coil motif. The hybrid peptide−DNA trimer was then used as a novel three-way junction to link together either small DNA tile nanostructures, or to close up a triangular wireframe DNA structure. The resulting nanostructures were characterized by atomic force microscopy, and compared with a scrambled, non-assembling peptide as a control. These hybrid nanostructures enable the integration of peptide motifs and potentially bio-functionality with DNA nanostructures, and open the door to novel nano-materials that have the advantages of both molecules.     

Self-Assembly of Nanostructures on Surfaces Using Metal–Organic Coordination

Layer-by-layer (LbL) assembly of multilayers is an established method for the construction of layered nanostructures on surfaces, affording control of the thickness, composition, and organization in the vertical direction. Binding between layers is accomplished using various types of interactions, including electrostatic binding, hydrogen bonding, covalent bonding, metal–organic coordination, host–guest interactions, biospecific interactions, and others. Here we focus on LbL assembly using metal–organic coordination, and specifically on layered nanostructures based on bishydroxamate–M⁴⁺ binding. The coordination approach offers attractive features, such as a simple reaction, a defined geometry, and reversibility under certain conditions. The basic scheme includes self-assembly of a ligand (anchor) monolayer on the surface, followed by alternate binding of metal ions and multi-functional ligand layers, to form a coordination multilayer. This approach is demonstrated by the construction of a variety of coordinated nanostructures, including bilayers, multilayers, dendrimers, and nanoparticle assemblies, prepared on gold and oxide substrates.     

Effect of Bay Regions on the Total π-Electron Energy of Benzenoid Hydrocarbons

The three main structural factors determining the total π-electron energy (E) of a benzenoid hydrocarbon are the number of C atoms (n), number of CC bonds (m) and the Kekulé structure count (K). Nevertheless, the E-values of benzenoid hydrocarbons having the same n, m and K may considerably vary. These variations are studied and found to depend on certain structural features of the perimeter, in particular on the number of bay regions (b). A linear relation between E and b is established, such that E increases with b. Furthermore, the effect of bay regions on E increases with the increasing size of the molecule.     

Self-Assembly and Neurotoxicity of β-Amyloid (21–40) Peptide Fragment: The Regulatory Role of GxxxG Motifs

The three GxxxG repeating motifs from the C-terminal region of β-amyloid (Aβ) peptide play a significant role in regulating the aggregation kinetics of the peptide. Mutation of these glycine residues to leucine greatly accelerates the fibrillation process but generates a varied toxicity profile. Using an array of biophysical techniques, we demonstrated the uniqueness of the composite glycine residues in these structural repeats. We used solvent relaxation NMR spectroscopy to investigate the role played by the surrounding water molecules in determining the corresponding aggregation pathway. Notably, the conformational changes induced by Gly³³ and Gly³⁷ mutations result in significantly decreased toxicity in a neuronal cell line. Our results indicate that G³³xxxG³⁷ is the primary motif responsible for Aβ neurotoxicity, hence providing a direct structure–function correlation. Targeting this motif, therefore, can be a promising strategy to prevent neuronal cell death associated with Alzheimer's and other related diseases, such as type II diabetes and Parkinson's.     

Decrease of carbon nanotube UV light absorption induced by π-π-stacking interaction with nucleotide bases

UV-vis absorption spectra of hybrids formed by carbon single-walled nanotubes (SWCNTs) and single-stranded DNA (ss-DNA), double-stranded DNA (ds-DNA), and synthetic homopolynucleotides (poly(rC) and poly(rG)) have been studied. In the 300-400 nm spectral range a decrease of SWCNT light absorption because of their interaction with polymers was observed. The revealed decrease of nanotube absorption is explained by SWCNT hypochromism that results from π-π-stacking interaction of polymer nitrogen bases with the tube surface. Molecular dynamic simulation demonstrates a spontaneous wrapping of polynucleotides around the nanotube. Simulation showed that pyrimidine oligonucleotide (d(C)₂₅) manifests a higher rate of minimizing the hybrid structure with the wrapped polymer structure around the tube than the purine one (d(G)₂₅). Such polymer behavior can be explained by the purine oligonucleotide property to form a stable ordering self-stacking structure which prevents structural re-orientation, in contrast to pyrimidine polynucleotides.     

Molecular dynamics simulation study on π-π stacking of Gemini surfactants in oil/water systems

Whereas the π-π stacking interactions at oil/water interfaces can affect interfacial structures hence the interfacial properties,the underlying microscopic mechanism remains largely unknown.We reported an all-atom molecular dynamics(MD) simulation study to demonstrate how the Gemini surfactants with pyrenyl groups affect the interracial properties,structural conformations,and the motion of molecules in the water/n-octane/surfactant ternary systems.It is found that the pyrenyl groups tend to be v...     

FRET-Based In-Cell Detection of Highly Selective Supramolecular Complexes of meso-Tetraarylporphyrin with Peptide/BODIPY-Modified Per-O-Methyl-β-Cyclodextrins

Artificial supramolecular systems capable of self-assembly and that precisely function in biological media are in high demand. Herein, we demonstrate a highly specific host-guest-pair system that functions in living cells. A per-O-methyl-β-cyclodextrin derivative (R8-B-CD^Me) bearing both an octaarginine peptide chain and a BODIPY dye was synthesized as a fluorescent intracellular delivery tool. R8-B-CD^Me was efficiently taken up by HeLa cells through both endocytosis and direct transmembrane pathways. R8-B-CD^Me formed a 2 : 1 inclusion complex with tetrakis(4-sulfonatophenyl)porphyrin (TPPS) as a guest molecule in water, from which fluorescence resonance energy transfer (FRET) from R8-B-CD^Me to TPPS was observed. The FRET phenomenon was clearly detected in living cells using confocal microscopy techniques, which revealed that the formed supramolecular R8-B-CD^Me/TPPS complex was maintained within the cells. The R8-B-CD^Me cytotoxicity assay revealed that the addition of TPPS counteracts the strong cytotoxicity (IC₅₀=16 μM) of the CD cavity due to complexation within the cells. A series of experiments demonstrated the bio-orthogonality of the supramolecular per-O-methyl-β-CD/tetraarylporphyrin host-guest pair in living cells.     

Supramolecular Assemblies of Cucurbiturils with Photoactive, π-conjugated Chromophores

Supramolecular assemblies of cucurbituril (CBn) homologues with π-conjugated chromophores will be overviewed. Special emphasis will be given to the effect of CBn on the optical properties of conjugated oligomers and polymers. How supramolecular complexes of π-conjugated chromophores including porphyrin derivatives, conjugated oligomers and polymers with CBn could be utilized in the theranostic and photonic applications will also be discussed.     

Molecular dynamics of carboxymethyl κ/ι-hybrid carrageenan films doped with NH4I

The effect of carboxymethylation and NH₄I incorporation on the molecular dynamics of carrageenan films was studied. Broadband Dielectric Spectroscopy (BDS) assessed the presence of α and β relaxation processes. The effect of NH₄I content was analyzed using the Havriliak-Negami model and parameterizing the temperature dependence of the relaxation times according to the Vogel-Fulcher-Tammann-Hesse (VFTH) equation. The glass transition temperature was found to decrease with the increase of NH₄I content. These results suggest that carboxymethylation and the salt doping treatment increase the molecular mobility of NH4+ ions, making the films suitable for the development of solid electrolytes for energy storage applications.     

Tuning the Solution Self-Assembly of a Peptide-PEG (Polyethylene Glycol) Conjugate with α-Cyclodextrin

Cyclodextrins are saccharide ring molecules which act as host cavities that can encapsulate small guest molecules or thread polymer chains. We investigate the influence of alpha-cyclodextrin (αCD) on the aqueous solution self-assembly of a peptide-polymer conjugate YYKLVFF-PEG3K previously studied by our group [Castelletto et al., Polym. Chem., 2010, 1, 453–459]. This conjugate comprises a designed amyloid-forming peptide YYKLVFF that contains the KLVFF sequence from Amyloid β peptide, Aβ16-20, along with two aromatic tyrosine residues to enhance hydrophobicity, as well as polyethylene glycol PEG with molar mass 3 kg mol⁻¹. The conjugate self-assembles into β-sheet fibrils in aqueous solution. Here we show that complexation with αCD instead generates free-floating nanosheets in aqueous solution (with a β-sheet structure). The nanosheets comprise a bilayer with a hydrophobic peptide core and highly swollen PEG outer layers. The transition from fibrils to nanosheets is driven by an increase in the number of αCD molecules threaded on the PEG chains, as determined by ¹H NMR spectroscopy. These findings point to the use of cyclodextrin additives as a powerful means to tune the solution self-assembly in peptide-polymer conjugates and potentially other polymer/biomolecular hybrids.     

CO Oxidation of Au–Pt Nanostructures: Enhancement of Catalytic Activity of Pt Nanoparticles by Au

The CO oxidation activity of Pt deposited on Ta₂O₅/Ta was studied with various amounts of Au post-deposited on Pt/Ta₂O₅/Ta. For Pt nanoparticles with a mean size of 2–4 nm, an enhancement in the CO oxidation activity with increasing amount of post-deposited Au was found. The mixed Au–Pt nanoparticles with sizes in the range of 2–4 nm exhibited higher stability than the bare Au nanoparticles with a similar size range. In contrast to the results obtained with the Pt nanoparticles, the catalytic activity of a thicker Pt film gradually decreased with increasing amount of Au deposited. Based on the CO desorption experiments, it is suggested that the surface of the catalytically active Au–Pt bimetallic structures consists of both Au and Pt sites.     

Evaluating π-π-Interactions as a Method for Isolation of Polycyclic Aromatic Hydrocarbons from Solution

The polycyclic aromatic hydrocarbon (PAH), chrysene, was linked to the solid support TentaGel S-NH₂ via a linker by means of synthesis. The resulting product 4-(chrysene-1-yloxy)-N-(TentaGel S)butanamide (4) was then evaluated for its ability to isolate PAHs from solution by means of π-π-interactions.     

Synthesis of new N, N-diphenylhydrazone dyes for solar cells: Effects of thiophene-derived π-conjugated bridge

Four novel D-π-A hydrazone dyes (HT, HM, HE, and HO) with an N, N-diphenylhydrazone moiety as the electron donor, different thiophene-derived π-conjugated bridges and a cyanoacrylic acid moiety as the electron acceptor have been designed and synthesized for the application in dye-sensitized solar cells. The influences of thiophene-derived bridges on the photoelectrochemical and photovoltaic performance of these hydrazone dyes were investigated. Results demonstrate that the introduction of 3,4-dialkyloxythiophene could red-shift the dye’s absorption spectrum due to the enhancement of the electron-donating ability of π-conjugated bridges. Importantly, electrochemical impedance spectroscopy analysis reveal that 3,4-dialkyloxythiophene bridge could change the charge recombination resistance at the TiO₂/dye/electrolyte interface and as a result to improve the open-circuit photovoltage. Among the four dyes, HO exhibits the maximum power conversion efficiency of 5.83% (V_oc = 0.65 V, J_sc = 12.69 mA/cm², FF = 0.707) under simulated AM 1.5 irradiation (100 mW/cm²).     

Combined 3D-QSAR, Molecular Docking and Molecular Dynamics Study on Derivatives of Peptide Epoxyketone and Tyropeptin-Boronic Acid as Inhibitors Against the β5 Subunit of Human 20S Proteasome

An abnormal ubiquitin-proteasome is found in many human diseases, especially in cancer, and has received extensive attention as a promising therapeutic target in recent years. In this work, several in silico models have been built with two classes of proteasome inhibitors (PIs) by using 3D-QSAR, homology modeling, molecular docking and molecular dynamics (MD) simulations. The study resulted in two types of satisfactory 3D-QSAR models, i.e., the CoMFA model (Q(2) = 0.462, R(2) (pred) = 0.820) for epoxyketone inhibitors (EPK) and the CoMSIA model (Q(2) = 0.622, R(2) (pred) = 0.821) for tyropeptin-boronic acid derivatives (TBA). From the contour maps, some key structural factors responsible for the activity of these two series of PIs are revealed. For EPK inhibitors, the N-cap part should have higher electropositivity; a large substituent such as a benzene ring is favored at the C6-position. In terms of TBA inhibitors, hydrophobic substituents with a larger size anisole group are preferential at the C8-position; higher electropositive substituents like a naphthalene group at the C3-position can enhance the activity of the drug by providing hydrogen bond interaction with the protein target. Molecular docking disclosed that residues Thr60, Thr80, Gly106 and Ser189 play a pivotal role in maintaining the drug-target interactions, which are consistent with the contour maps. MD simulations further indicated that the binding modes of each conformation derived from docking is stable and in accord with the corresponding structure extracted from MD simulation overall. These results can offer useful theoretical references for designing more potent PIs.     

Doping behavior of water-soluble π-conjugated polythiophenes depending on pH and interaction of the polymer with DNA

Doping behavior of two kinds of water-soluble polythiophenes (PThs) (PTh with a CH₂CH₂CH₂SO₃M substituent at the 3-position, P3(RSO₃H)Th, and poly(ethylenedioxythiophene), PEDOTh) has been investigated spectroscopically at various pH under air. The p-doped (or oxidized) state of P3(RSO₃M)Th is stable at pH=1.0, whereas at pH levels higher than 4, the polymer is undoped. To the contrary, the p-doped state of PEDOTh is stable over a pH range of 1 to 7. Mixing of PEDOTh and a DNA (poly(G-C)₂) in a Tris buffer solution leads to a change of the UV-visible spectrum and precipitation of their adduct, supporting formation of an adduct between PEDOTh and poly(G-C)₂.     

Turn-Directed α-β Conformational Transition of α-syn12 Peptide at Different pH Revealed by Unbiased Molecular Dynamics Simulations

The transition from α-helical to β-hairpin conformations of α-syn12 peptide is characterized here using long timescale, unbiased molecular dynamics (MD) simulations in explicit solvent models at physiological and acidic pH values. Four independent normal MD trajectories, each 2500 ns, are performed at 300 K using the GROMOS 43A1 force field and SPC water model. The most clustered structures at both pH values are β-hairpin but with different turns and hydrogen bonds. Turn_9-6 and four hydrogen bonds (HB_9-6, HB_6-9, HB_11-4 and HB_4-11) are formed at physiological pH; turn_8-5 and five hydrogen bonds (HB_8-5, HB_5-8, HB_10-3, HB_3-10 and HB_12-1) are formed at acidic pH. A common folding mechanism is observed: the formation of the turn is always before the formation of the hydrogen bonds, which means the turn is always found to be the major determinant in initiating the transition process. Furthermore, two transition paths are observed at physiological pH. One of the transition paths tends to form the most-clustered turn and improper hydrogen bonds at the beginning, and then form the most-clustered hydrogen bonds. Another transition path tends to form the most-clustered turn, and turn_5-2 firstly, followed by the formation of part hydrogen bonds, then turn_5-2 is extended and more hydrogen bonds are formed. The transition path at acidic pH is as the same as the first path described at physiological pH.     

Synthesis of the Ni–Al–C Composite with Multilayer Carbon Nanostructures by an Electrothermal Explosion under Pressure

Combustion, Explosion, and Shock Waves - A composite material based on the Ni–Al–C system is synthesized by the method of an electrothermal explosion at a pressure of 96 MPa. During the...     

Preparation and properties of new π-conjugated polyquinoxalines with aromatic fused rings in the side chain

Summary New π-conjugated polyquinoxalines with aromatic fused rings in their side chain have been prepared. Dehalogenative organometallic polycondensation of 5,8-dibromo[2,3-b]-acenaphthenequinoxaline and 5,8-dibromo[2,3-b]phenanthrenequinoxaline with a zerovalent nickel complex afforded poly([2,3-b]acenaphthenequinoxaline-5,8-diyl) (P(5,8-Qx(ace))) and poly([2,3-b]phenanthrenequinoxaline-5-8-diyl) (P(5,8-Qx(phen))) in high yields. P(5, 8-Qx(ace)) had an [η] value of 0.23 dL g⁻¹ and showed absorption and photoluminescence peaks at 445 and 565 nm, respectively. (P(5,8-Qx(phen))) gave absorption and photoluminescence peaks at 400 and 514 nm, respectively. XRD data indicated formation of ordered structures of the polymers in the solid. Preparation of related copolymer with thiophene is also reported. Received: 15 February 2000/Accepted: 2 March 2000     

Low-bandgap copolymers consisting of 2,1,3-benzoselenadiazole and carbazole derivatives with thiophene or selenophene π-bridges

Two donor–acceptor-type alternating copolymers consisting of 2,1,3-benzoselenadiazole and carbazole derivatives with thiophene or selenophene π-bridges were synthesized by Suzuki cross-coupling polymerization, and their optical, electrochemical, and photovoltaic properties were compared. The selenophene π-bridged copolymer (PCz-DSeBSe) exhibited a smaller band-gap (1.82 eV) than the thiophene-bridged polymer (PCz-DTBSe; 1.89 eV). PCz-DSeBSe also showed a deeper highest occupied molecular orbital energy level (−5.36 eV) than PCz-DTBSe (−5.20 eV). Moreover, the PCz-DSeBSe thin film showed higher crystallinity and hole mobility than the PCz-DTBSe thin film. Organic photovoltaic devices were fabricated using the polymers as the donors and [6,6]-phenyl-C₇₁-butyric acid methyl ester (PC₇₁BM) as the acceptor. The device using PCz-DSeBSe showed a higher open circuit voltage (V_oc), short circuit current density (J_sc), and power conversion efficiency (PCE) than that using PCz-DTBSe. The fabricated indium tin oxide/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)/PCz-DSeBSe:PC₇₁BM/LiF/Al device showed the maximum PCE of 2.88% with a J_sc of 7.87 mA/cm², an V_oc of 0.80 V, and a fill factor of 0.50 under AM 1.5G irradiation (100 mW/cm²).     

Assessing the Effect of Loop Mutations in the Folding Space of β2-Microglobulin with Molecular Dynamics Simulations

We use molecular dynamics simulations of a full atomistic Gō model to explore the impact of selected DE-loop mutations (D59P and W60C) on the folding space of protein human β₂-microglobulin (Hβ₂m), the causing agent of dialysis-related amyloidosis, a conformational disorder characterized by the deposition of insoluble amyloid fibrils in the osteoarticular system. Our simulations replicate the effect of mutations on the thermal stability that is observed in experiments in vitro. Furthermore, they predict the population of a partially folded state, with 60% of native internal free energy, which is akin to a molten globule. In the intermediate state, the solvent accessible surface area increases up to 40 times relative to the native state in 38% of the hydrophobic core residues, indicating that the identified species has aggregation potential. The intermediate state preserves the disulfide bond established between residue Cys25 and residue Cys80, which helps maintain the integrity of the core region, and is characterized by having two unstructured termini. The movements of the termini dominate the essential modes of the intermediate state, and exhibit the largest displacements in the D59P mutant, which is the most aggregation prone variant. PROPKA predictions of pK_a suggest that the population of the intermediate state may be enhanced at acidic pH explaining the larger amyloidogenic potential observed in vitro at low pH for the WT protein and mutant forms.