β to β Terpyridylene-bridged porphyrin nanorings

β β to Terpyridine bridged cyclic porphyrin dimer, trimer, tetramer and pentamer were obtained through one-pot Suzuki-Miyaura crossing coupling reaction in good yields with template free. These porphyrin nanorings possess high fluorescence quantum yields and large extinction coefficients.     

Phase networks of cross-β peptide assemblies

Recent evidence suggests that simple peptides can access diverse amphiphilic phases, and that these structures underlie the robust and widely distributed assemblies implicated in nearly 40 protein misfolding diseases. Here we exploit a minimal nucleating core of the Aβ peptide of Alzheimer's disease to map its morphologically accessible phases that include stable intermolecular molten particles, fibers, twisted and helical ribbons, and nanotubes. Analyses with both fluorescence lifetime imaging microscopy (FLIM) and transmission electron microscopy provide evidence for liquid-liquid phase separations, similar to the coexisting dilute and dense protein-rich liquid phases so critical for the liquid-solid transition in protein crystallization. We show that the observed particles are critical for transitions to the more ordered cross-β peptide phases, which are prevalent in all amyloid assemblies, and identify specific conditions that arrest assembly at the phase boundaries. We have identified a size dependence of the particles in order to transition to the para-crystalline phase and a width of the cross-β assemblies that defines the transition between twisted fibers and helically coiled ribbons. These experimental results reveal an interconnected network of increasing molecularly ordered cross-β transitions, greatly extending the initial computational models for cross-β assemblies.     

Physico-chemical Characterization of Mo-Hβ Zeolite Catalysts

A series of Mo-impregnated Hβ samples, with MoO3 loading in Hβ zeolite in the mass fraction range of 0. 5%-6.0%, were studied by means of XRD and IR in order to characterize their structures. Mo/Hβ sampies‘ crystallinity almost linearly decreases with increasing the amount of MoO3 loaded, The IR spectra and XRD patterns suggest that the progressive destabilization of the Hβ zeolite structure is caused by increasing Mo loading in (MoO3 Hβ zeolite). During the calcination, Al2(MoO4)3 formed from the dealumination of Hβ zeolite, causes the substantially partial breakdown of the zeolite framework when the Mo loading in MoO3 Hβ is relatively high.     

Physico-chemical Characterization of Mo-Hβ Zeolite Catalysts

A series of Mo-impregnated Hβ samples, with MoO3 loading in Hβ zeolite in the mass fraction range of 0. 5%-6.0%, were studied by means of XRD and IR in order to characterize their structures. Mo/Hβ samples' crystallinity almost linearly decreases with increasing the amount of MoO3 loaded. The IR spectra and XRD patterns suggest that the progressive destabilization of the Hβ zeolite structure is caused by increasing Mo loading in (MoO3 Hβ zeolite). During the calcination, Al2(MoO4)3 formed from the dealumination of Hβ zeolite, causes the substantially partial breakdown of the zeolite framework when the Mo loading in MoO3 Hβ is relatively high.     

Cu K-edge X-ray absorption spectroscopy reveals differential copper coordination within amyloid-β oligomers compared to amyloid-β monomers

The fatal neurological disorder Alzheimer's disease has been linked to soluble neurotoxic oligomers of amyloid-β (Aβ) peptides. Herein we demonstrate that Cu(1+) ligated within Aβ(42) oligomers (Aβ sequence: DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA) possesses a highly dioxygen sensitive tetrahedral coordination geometry. The biological implications of these findings are discussed.     

Aluminium Mediated Glycosaminoglycan/Amyloid-β Association Mechanism

In Alzheimer’s disease, it has been proposed that glycosaminoglycans facilitate amyloid fibril formation and/or stabilize the plaque aggregates. Chondroitin sulfates are sulfated glycosaminoglycans represented an ideal distribution of charge for amyloid-β (Aβ) interactions. Recent studies have suggested a possible link between the neurotoxicity of aluminum and the pathogenesis of Alzheimer’s disease. In this paper, the interaction of Aβ with chondroitin sulfates immobilized on a chromatographic column and the role of aluminum had been studied using a biochromatographic approach (molecular chromatography). A novel biochromatographic column was developed in our laboratory for studying this interaction. This study demonstrated that the aluminum interacted with Aβ and played a role in the Aβ/chondroitin sulfates association. For a Al³⁺ concentration (x) in the medium less than 30 μmM, the Aβ/chondroitin sulfates binding decreased with x due to a decrease of the charge–charge interactions between Aβ and its chondroitin sulfates binding site. Above 30 μmM of Al³⁺ in the medium, the affinity of Aβ to chondroitin sulfates increased slightly with x because the net number of ions (n) (Al³⁺ or Cl^?) released or bound upon complex formation is low. As well, it was clearly demonstrated, that above 30 μmM the n value depend on the Al³⁺ concentration in the bulk solvent. This dependence was due to a gradual and conformational change of the Aβ which around 80 μmM adopted a less flexible structure; its binding site was thus less accessible to Aβ and Aβ/chondroitin sulfates association decreased slightly.     

β'β Anionic elimination of carboxylic esters

The elimination of lithium, magnesium and aluminium enolatea of isobutyrates of medium ring cyclanols occurs in a syn fashion. A set of experimental procedures is presented. This elimination seems to be restricted to strained systems. The stereo-chemistry has been determined on stereospecifically deuterated cyclooctanol isobutyrates. The primary isotope effect k_H/k₂ was 3.0 ± 0.1 and the secondary 1.1. The name β'β elimination is proposed for this syn elimination and related elimination.     

Stability of amyloid-β peptides in plasma and serum

Plasma amyloid‐β peptide (Aβ) levels have been suggested as a biomarker candidate for detecting incipient AD. Aβ peptides are known to be sensitive to distinct preanalytical sample handling, which calls for standardised preanalytical procedures. We investigated serum and plasma samples of 19 patients with no clinical signs of dementia for different preanalytical sample handlings. Both serum and plasma were analysed by the one‐dimensional Aβ‐SDS‐PAGE/immunoblot, either immediately or after storage at room temperature for 24 and 48 h, respectively. The panel of Aβ1–37/38/39/40/42 and Aβ2–40 was evaluated. In both analytical matrices, sample storage led to a significant loss of measurable peptide levels. This effect was most pronounced during the first 24 h of storage and stronger in serum than in plasma. There were no significant differences between the distinct analysed Aβ peptide species regarding these results. The ratios of peptides (e.g. Aβ1–42/Aβ1–40 and Aβ1–42/Aβ1–38) displayed a higher stability under the influence of storage than each single peptide. In conclusion, plasma may be more appropriate than serum for analysing Aβ peptides for routine application. At least, the analysis should be done within 24 h and peptide ratios should be created to minimise artificial results.     

cis-Glyco-fused benzopyran compounds as new amyloid-β peptide ligands

A small library of glyco-fused benzopyran compounds has been synthesised. Their interaction features with Aβ peptides have been characterised by using STD-NMR and trNOESY experiments. The conformational analysis of the compounds has also been carried out through molecular mechanics (MM) and molecular dynamics (MD) simulations.     

Evaluation of Aβ fibrillization inhibitory effect by a PEG-peptide conjugate based on an Aβ peptide fragment with intramolecular FRET

A PEG-peptide conjugate based on an amyloid β peptide fragment was synthesized. The formed amyloid protofibril-like aggregates induced intramolecular FRET. It proved to be useful as a bioprobe to evaluate the inhibitory effect of organic molecules toward amyloid fibrillization.     

Synthesis of β -chloro- and β ,β -dichlorovinylalkyldichlorosilanes

Summary A simple method of synthesis of , -dichlorovinylalkyldichlorosilanes was developed, and their alkyl and alkoxy derivatives were prepared.     

Temperature dependence of the cristobalite α-β inversion

The cristobalite - inversion has been studied using DSC on cristobalites produced by firing high purity quartz with and without addition of a mineraliser. If no mineraliser was used, the inversion temperatures and hysteresis on heating and cooling increased with firing temperature. Firing time had little or no effect on inversion temperature. When a mineraliser was used, the same general trend was observed with increases in firing time at low temperatures leading to splitting of the inversion peak. The amount of mineraliser added had little effect. Tridymite inversions were also observed. The results are explained in terms of the degree of order of the cristobalite structure.We are grateful for the award of an S.E.R.C. CASE award in conjunction with Specialist Refractory Services to SJS. Helpful discussions have been held with Mr. D. W. Bailey and Dr. P. Watkins.     

α-β Phase Re-Transformation Kinetics in Nickel Sulphide

Nickel sulphide (NiS) was characterised using X-ray diffraction, thermal gravimetric analysis (TG) and differential scanning calorimetry (DSC). The 'as received' Millerite, stoichiometric NiS, observed to be slightly nickel deficient, was found to readily decompose in a nitrogen atmosphere at elevated temperatures (450°C max.) to the sulphur deficient Godlevskite, Ni₇S₆. DSC and X-ray measurements demonstrated that the high temperature form of the Godlevskite was readily stabilised at room temperature. The kinetics of the α-β re-transformation in Godlevskite were then investigated using DSC and were observed to be first order. This revised version was published online in July 2006 with corrections to the Cover Date.     

Strategies for Inhibition and Disaggregation of Amyloid-β Fibrillation

Amyloid-β protein(Aβ)is a fatal cause of Alzheimer's disease,which can trigger a series of cytotoxicity by the abnormal aggregation of Aβ in human brain.The str...     

Diastereoselective conjugate addition to chiral α,β ethylenic acetals

The phenyl copper reagent associated with Lewis acid (BP₃) reacts regio (SN₂′) and stereoselectively with chiral α,β ethylenic acetals.     

A novel mass spectrometry-based assay for GSK-3β activity

Background  

As a component of the progression from genomic to proteomic analysis, there is a need for accurate assessment of protein post-translational modifications such as phosphorylation. Traditional kinase assays rely heavily on the incorporation of γ-P³² radiolabeled isotopes, monoclonal anti-phospho-protein antibodies, or gel shift analysis of substrate proteins. In addition to the expensive and time consuming nature of these methods, the use of radio-ligands imposes restrictions based on the half-life of the radionucleotides and pose potential health risks to researchers. With the shortcomings of traditional assays in mind, the aim of this study was to develop a high throughput, non-radioactive kinase assay for screening Glycogen Synthase Kinase-3beta (GSK-3β) activity.     

Development of a Protein Chip to Measure PKCβ Activity

Phosphorylation of proteins by kinases plays an important role in regulating cellular processes including melanin production in the skin cells. Protein kinase C β (PKCβ) is known to be involved in phosphorylating tyrosinase, the key enzyme of melanin production, regulating the skin pigmentation process. In melanogenesis, PKCβ activates the tyrosinase by phosphorylation of its two serine residues. In this study, phosphorylation activity by PKCβ was monitored on a protein chip for the screening of depigmenting agents. As a tyrosinase mimic, 11 or 30 amino acids of the C-terminal of tyrosinase was fused with maltose-binding protein (MBP). After immobilizing the MBP-fused PKCβ substrate peptide on epoxy-treated slide surface, PKCβ reaction mix was applied over the immobilized MBP-fused PKCβ substrate peptide. Phosphorylation was detected with anti-phosphoSer/Thr antibodies, followed by fluorescence-labeled second antibodies. Phosphorylation of MBP-30aa was observed on a protein chip, and this phosphorylation was inhibited by the PKC inhibitor (GF109203X). These results indicate the potential of PKCβ protein chip as a high-throughput screening tool in the screening of depigmenting agents.