Design and self-assembly of a leucine-enkephalin analogue in different nanostructures: application of nanovesicles

An opioid (leucine-enkephalin) conformational analogue forms diverse nanostructures such as vesicles, tubes, and organogels through self-assembly. The nanovesicles encapsulate the natural hydrophobic drug curcumin and allow the controlled release through cation-generated porogens in membrane mimetic solvent.

Formation of vesicles through solvent assisted self-assembly of hydrophobic pentapeptides: encapsulation and pH responsive release of dyes by the vesicles

In the biomimetic design two hydrophobic pentapetides Boc-Ile-Aib-Leu-Phe-Ala-OMe ( I) and Boc-Gly-Ile-Aib-Leu-Phe-OMe (II) (Aib: alpha-aminoisobutyric acid) containing one Aib each are found to undergo solvent assisted self-assembly in methanol/water to form vesicular structures, which can be disrupted by simple addition of acid. The nanovesicles are found to encapsulate dye molecules that can be released by the addition of acid as confirmed by fluorescence microscopy and UV studies. The influence of solvent polarity on the morphology of the materials generated from the peptides has been examined systematically, and shows that fibrillar structures are formed in less polar chloroform/petroleum ether mixture and vesicular structures are formed in more polar methanol/water. Single crystal X-ray diffraction studies reveal that while beta-sheet mediated self-assembly leads to the formation of fibrillar structures, the solvated beta-sheet structure leads to the formation of vesicular structures. The results demonstrate that even hydrophobic peptides can generate vesicular structures from polar solvent which may be employed in model studies of complex biological phenomena.

Pairwise assembly of organopalladium(II) units with cyanurato(3-) and trithiocyanurato(3-) ligands: formation of chiral Pd12, Pd10 and Pd9 cage-molecules

The o-palladated, chloro-bridged dimers [Pd{2-phenylpyridine(-H)}-μ-Cl]2 and [Pd{N,N-dimethylbenzylamine(-H)}-μ-Cl]2 react with cyanuric acid in the presence of base to afford closed, chiral cage-molecules in which twelve organo-Pd(II) centers, located in pairs at the vertices of an octahedron, are linked by four tetrahedrally-arranged cyanurato(3-) ligands. Incomplete (Pd10) cages, having structures derived from the corresponding Pd12 cages by replacing one pair of organopalladium centers with two protons, have also been isolated. Reaction of [Pd{2-phenylpyridine(-H)}-μ-Cl]2 with trithiocyanuric acid gives an entirely different and more open type of cage-complex, comprising only nine organopalladium centers and three thiocyanurato(3-) ligands: cage-closure in this latter system appears to be inhibited by steric crowding of the thiocarbonyl groups.

Self-assembly and bioactivity of a polymer/peptide conjugate containing the RGD cell adhesion motif and PEG

The self-assembly and bioactivity of the peptide–polymer conjugate DGRFFF–PEG3000 containing the RGD cell adhesion motif has been examined, in aqueous solution. The conjugate is designed to be amphiphilic by incorporation of three hydrophobic phenylalanine residues as well as the RGD unit and a short poly(ethylene glycol) (PEG) chain of molar mass 3000 kg mol-1. Above a critical aggregation concentration, determined by fluorescence measurements, signals of b-sheet structure are revealed by spectroscopic measurements, as well as X-ray diffraction. At high concentration, a self-assembled fibril nanostructure is revealed by electron microscopy. The fibrils are observed despite PEG crystallization which occurs on drying. This suggests that DGRFFF has an aggregation tendency that is sufficiently strong not to be prevented by PEG crystallization. The adhesion, viability and proliferation of human corneal fibroblasts was examined for films of the conjugate on tissue culture plates (TCPs) as well as low attachment plates. On TCP, DGRFFF–PEG3000 films prepared at sufficiently low concentration are viable, and cell proliferation is observed. However, on low attachment surfaces, neither cell adhesion nor proliferation was observed, indicating that the RGD motif was not available to enhance cell adhesion. This was ascribed to the core–shell architecture of the self-assembled fibrils with a peptide core surrounded by a PEG shell which hinders access to the RGD unit.

Self-assembly of a Model Peptide incorporating a Hexa-Histidine sequence attached to an Oligo-Alanine sequence, and binding to Gold NTA/Nickel nanoparticles

Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexahistidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cac’s), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of prefibrillar structures, whereas a millimolar range cac is associated with the formation of well-defined but more compact fibrils. We examine the labeling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labeling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the β-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/nanoparticle hybrid materials.

Self-assembly of a dual functional bioactive peptide amphiphile incorporating both matrix metalloprotease substrate and cell adhesion motifs

We describe a bioactive lipopeptide that combines the capacity to promote the adhesion and subsequent self-detachment of live cells, using template-cell-environment feedback interactions. This self-assembling peptide amphiphile comprises a diene-containing hexadecyl lipid chain (C16e) linked to a matrix metalloprotease-cleavable sequence, Thr-Pro-Gly-Pro-Gln-Gly-Ile-Ala-Gly-Gln, and contiguous with a cell-attachment and signalling motif, Arg-Gly-Asp-Ser. Biophysical characterisation revealed that the PA self-assembles into 3 nm diameter spherical micelles above a critical aggregation concentration (cac). In addition, when used in solution at 5–150 nM (well below the cac), the PA is capable of forming film coatings that provide a stable surface for human corneal fibroblasts to attach and grow. Furthermore, these coatings were demonstrated to be sensitive to metalloproteases expressed endogenously by the attached cells, and consequently to elicit the controlled detachment of cells without compromising their viability. As such, this material constitutes a novel class of multi-functional coating for both fundamental and clinical applications in tissue engineering.

Self-assembly of telechelic tyrosine end-capped PEO and poly(alanine) polymers in aqueous solution

The self-assembly in aqueous solution of three novel telechelic conjugates comprising a central hydrophilic polymer and short (trimeric or pentameric) tyrosine end-caps has been investigated. Two of the conjugates have a central poly(oxyethylene) (polyethylene oxide, PEO) central block with different molar masses. The other conjugate has a central poly(l-alanine) (PAla) sequence in a purely amino-acid based conjugate. All three conjugates self-assemble into β-sheet based fibrillar structures, although the fibrillar morphology revealed by cryogenic-TEM is distinct for the three polymers—in particular the Tyr5-PEO6k-Tyr5 forms a population of short straight fibrils in contrast to the more diffuse fibril aggregates observed for Tyr5-PEO2k-Tyr5 and Tyr3-PAla-Tyr3. Hydrogel formation was not observed for these samples (in contrast to prior work on related systems) up to quite high concentrations, showing that it is possible to prepare solutions of peptide–polymer-peptide conjugates with hydrophobic end-caps without conformational constraints associated with hydrogelation. The Tyr5-PEO6k-Tyr5 shows significant PEO crystallization upon drying in contrast to the Tyr5-PEO2k-Tyr5 conjugate. Our findings point to the remarkable ability of short hydrophobic peptide end groups to modulate the self-assembly properties of polymers in solution in model peptide-capped “associative polymers”. Retention of fluidity at high conjugate concentration may be valuable in potential future applications of these conjugates as bioresponsive or biocompatible materials, for example exploiting the enzyme-responsiveness of the tyrosine end-groups

Hepatic denervation impairs the assembly and secretion of VLDL-TAG

VLDL secretion is a regulated process that depends on the availability of lipids, apoB and MTP. Our aim was to investigate the effect of liver denervation upon the secretion of VLDL and the expression of proteins involved in this process. Denervation was achieved by applying a 85% phenol solution onto the portal tract, while control animals were treated with 9% NaCl. VLDL secretion was evaluated by the Tyloxapol method. The hepatic concentration of TAG and cholesterol, and the plasma concentration of TAG, cholesterol, VLDL-TAG, VLDL-cholesterol and HDL-cholesterol were measured, as well as mRNA expression of proteins involved in the process of VLDL assembly. Hepatic acinar distribution of MTP and apoB was evaluated by immunohistochemistry. Denervation increased plasma concentration of cholesterol (125.3 +/- 10.1 vs. 67.1 +/- 4.9 mg dL(-1)) and VLDL-cholesterol (61.6 +/- 5.6 vs. 29.4 +/- 3.3 mg dL(-1)), but HDL-cholesterol was unchanged (45.5 +/- 6.1 vs. 36.9 +/- 3.9 mg dL(-1)). Secretion of VLDL-TAG (47.5 +/- 23.8 vs. 148.5 +/- 27.4 mg dL h(-1)) and mRNA expression of CPT I and apoB were reduced (p < 0.01) in the denervated animals. MTP and apoB acinar distribution was not altered in the denervated animals, but the intensity of the reaction was reduced in relation to controls. Copyright (C) 2008 John Wiley & Sons, Ltd.

Hierarchical Assembly of CaMoO(4) Nano-Octahedrons and Their Photoluminescence Properties

Hierarchical assemblies of CaMoO4 (CM) nano-octahedrons were obtained by microwave-assisted hydrothemial synthesis at 120 degrees C for different times. These structures were structurally, morphologically and optically characterized by X-ray diffraction, micro-Raman spectroscopy, field-emission gun scanning electron microscopy, ultraviolet-visible absorption spectroscopy and photoluminescence measurements. First-principle calculations have been carried out to understand the structural and electronic order-disorder effects as a function of the particle/region size. Supercells of different dimensions were constructed to simulate the geometric distortions along both they and z planes of the scheelite structure. Based on these experimental results and with the help of detailed structural simulations, we were able to model the nature of the order-disorder in this important class of materials and discuss the consequent implications on its physical properties, in particular, the photoluminescence properties of CM nanocrystals.

On the relationships between molecular conformations and intermolecular contacts toward crystal self-assembly of mono-, di-, tri-, and tetra-oxygenated xanthone derivatives

Oxygenated xanthones have been extensively investigated over the years, but there are few reports concerning their crystal structure. Our chemical investigations of Brazilian plants resulted in the isolation of four natural products named 1-hydroxyxanthone (I), 1-hydroxy-7-methoxyxanthone (II), 1,5-dihydroxy-3-methoxyxanthone (III), and 1,7-dihydroxy-3,8-dimethoxyxanthone (IV). The structures of these compounds were established on the basis of single crystal X-ray diffraction. The xanthone nucleus conformation is essentially planar with the substituents adopting the orientations less sterically hindered. In addition, classical intermolecular hydrogen bonds (O-H center dot center dot center dot O) present in III and IV give rise to infinite ribbons. However, the xanthone I does not present any intermolecular hydrogen bonds, meanwhile the xanthone II presents only a non-classical one (C-H center dot center dot center dot O). The crystal packing of all xanthone structures is also stabilized by pi-pi interactions. The fingerprint plots, derived from the Hirshfeld surfaces, exhibited significant features of each crystal structures.

Cambrian mafic to felsic magmatism and its connections with transcurrent shear zones of the Borborema Province (NE Brazil): Implications for the late assembly of the West Gondwana

New U-Pb (SHRIMP) and (40)Ar/(39)Ar isotopic data of igneous rocks and mylonites of the Borborema Province (NE Brazil) show that a wide range of tectonothermal events affected the province during the transition from the Precambrian to the Cambrian. Concordant zircon U-Pb data constrained the crystallization age of mafic stocks, mafic to felsic dikes and granite batholiths between 548 and 533 Ma. These bodies were emplaced in a regional strain field combining extension and dextral shearing. The ductile shear deformation overprinted an older basement fabric to develop a low- to medium metamorphic grade vertical mylonite belt that cut the province in the E-W direction. Magnetic fabrics of the Cambrian batholiths determined by anisotropy of magnetic susceptibility are consistent with syntectonic emplacement. The magmatic pulses and shear deformation would have supplied enough heat to reset the synkinematic micas of mylonites to yield (40)Ar/(39)Ar plateau cooling ages between ca. 550 and 510 Ma. These results provide evidence that emplacement of Early Cambrian mafic and felsic magmas were accompanied by regional-scale shear deformations, probably in the consequence of late collisions along the West Gondwana margin. (C) 2010 Published by Elsevier B.V.

Influence of education and depressive symptoms on cognitive function in the elderly

Objective: The purpose of the present study was to investigate the influence that education and depression have on the performance of elderly people in neuropsychological tests. Methods: The study was conducted at the Institute of Psychiatry, University of Sao Paulo School of Medicine, Hospital das Clinicas. All of the individuals evaluated were aged 60 or older. The study sample consisted of 59 outpatients with depressive disorders and 51 healthy controls. We stratified the sample by level of education: low = 1-4 years of schooling; high = 5 or more years of schooling. Evaluations consisted of psychiatric assessment, cognitive assessment, laboratory tests and cerebral magnetic resonance imaging. Results: We found that level of education influenced all the measures of cognitive domains investigated (intellectual efficiency, processing speed, attention, executive function and memory) except the Digit Span Forward and Fuld Object Memory Evaluation (immediate and delayed recall), whereas depressive symptoms influenced some measures of memory, attention, executive function and processing speed. Although the combination of a low level of education and depression had a significant negative influence on Stroop Test part B, Trail Making Test part B and Logical Memory (immediate recall), we found no other significant effects of the interaction between level of education and depression. Conclusion: The results of this study underscore the importance of considering the level of education in the analysis of cognitive performance in depressed elderly patients, as well as the relevance of developing new cognitive function tests in which level of education has a reduced impact on the results.