Rapid label-free detection of metal-induced Alzheimer’s amyloid β peptide aggregation by electrochemical method

Amyloid β peptide plays a critical role in the pathogenesis of Alzheimer’s disease (AD). Metal ions are highly enriched in cerebral amyloid deposits in AD and are proposed to be able to mediate Aβ conformation. Therefore, a rapid, low-cost, and sensitive detection of metal-induced Aβ aggregation and their relation to AD is clearly needed for the clinical diagnosis and treatment. In this report, we study metal-induced Aβ aggregation by a rapid, label-free electrochemical method and monitor both the aggregation kinetics and the morphology in the absence or presence of Zn (II) and Cu (II). Different electrochemical behaviors of Aβ in the absence or presence of metal ions have been observed both in the aggregation kinetics and final aggregates. Our results provide new insights into the application of the rapid, low-cost and sensitive electrochemical device for clinical diagnosis of metal effects on AD or other neurodegenerative diseases which are related to protein misfolding.     

Study on the interaction between baicalein and the amyloid β peptide by molecular spectroscopy

The amyloid β peptide (Aβ) is the major protein constituent of neuritic plaques in Alzheimer's disease (AD).And Aβ(1-42) is the major component in amyloid plaque core deposits.     

Optimized method for the recombinant production of a sea anemone’s peptide

The production of the analgesic peptide HCRG21 for medical use is restricted by a number of limitations in the technology. The optimal biotechnological method scalable to industrial has been developed based on the production of a fusion protein containing a special leader, His-tag, and Smt3 sequence upstream in the peptide sequence. The resulting peptide shared its inhibitory activity to TRPV1 ion channel identical to the published early.     

Paradigms and paradoxes: Hess’ law and the thermodynamic validity of Jolly’s method for estimating bond dissociation energies

This study evaluates Jolly’s method to estimate the difference in homolytic bond dissociation energy between two isoelectronic molecules by the use of atomic and ionic electronegativities. The use of intermediate species as an energetic “stepping stone” between the two diatomic species in question is discussed, particularly within the context of Hess’ law. We also show a sample calculation for a pair of diatomic species that is fully consistent with data from atomic physics.     

Strategies for examination of Alzheimer’s disease amyloid precursor protein isoforms

We describe a proteomics procedure using bioinformatics, immunoprecipitation, two-dimensional gel electrophoresis, Western blotting, in-gel digestion, LC–MS, MALDI–MS, and MS–MS for isolation and identification of amyloid precursor protein (APP) isoforms APP₆₉₅, APP₇₅₁, and APP₇₇₀. Retinoic acid-induced Ntera 2 cell line, derived from a human teratocarcinoma cells, was the in-vitro source of APP. Initial isolation of whole APP was performed by immunoprecipitation, using AB10, a monoclonal antibody raised to amino acids 1–17 of the β-amyloid peptide sequence, which is present in all three alpha secretase-cleaved isoforms of interest. The next stage was separation of whole APP into its isoform components by two-dimensional gel electrophoresis. Because of low APP concentrations, detection by the usual staining methods, for example Sypro Ruby, able to detect low picomole concentrations, did not enable visualisation of the isoforms. Western analysis, however, enabled primary detection of APP, because of the inherent sensitivity of antibodies raised to specific isoform regions. This initial visualization acted as a template for excision of isoforms from 2D gels, which were then subjected to peptide mass mapping. Initial theoretical digestion of each isoform revealed the presence of specific peptides, which were then used as “tags” for isoform detection.     

A kinetic and thermodynamic study of the α-cyclodextrin mediated reaction of a range of p-substituted phenyl methyl sulfides with binding and non-binding peroxyacids

This paper presents a thermodynamic study of the rate and equilibria processes involved in the α-cyclodextrin mediated reaction of a range of 4-substituted phenyl methyl sulfides with two peroxyacids of different binding affinities. The results for the inclusion processes show that the formation of 1:1 and 2:1 (host:guest) complexes between α-cyclodextrin and phenyl methyl sulfides are generally enthalpically controlled, particularly so for the 2:1 complexes, as might be expected for a ternary complex. The data from this series of sulfides is presented as enthalpy-entropy compensation plots, yielding slopes of unity for each inclusion process. The formation of a 1:1 complex between cyclodextrin and the strongly associating 3-chloroperbenzoic acid (MCPBA) is also enthapically controlled. The other peroxyacid used, peroxomonosulfate, does not bind to α-cyclodextrin to any measurable degree. As described in our original study of this reaction system (Davies and Deary in J Chem Soc Perkin Trans 2:2423–2430, 1996), catalysis by α-cyclodextrin is effected by activation of the peroxide as a result its inclusion within the cyclodextrin cavity; hence for reactions of phenyl methyl sulfides with MCPBA, catalysis is observed, but is absent for PMS. In this study the reaction rates are analysed using the transition state pseudo-equilibrium approach of Tee (Carbohydr Res 192:181–195, 1989), whereby the transition state pseudoequilibrium constant K _TS reflects the stabilisation imparted to the transition state by the association with one molecule of cyclodextrin. Enthalpy- entropy compensation plots for K _TS give slopes close to unity; this is the first reported example of such plots being applied to transition state pseudoequilibrium constants.     

A label-free MALDI TOF MS-based method for studying the kinetics and inhibitor screening of the Alzheimer’s disease drug target β-secretase

Analytical and Bioanalytical Chemistry - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) is a well-established method with a unique set of qualities...     

Comparison of the boundary theory with the contact rule of phase regions and Gupta’s method

1Introduction J.W.Gibbs’phase equilibrium theory,especially the phase rule,laid the foundation for the phase theory,but the phase rule cannot solve the problems regarding the relation between neighboring phase regions(ab-breviated to NPRs)and their bound…     

A study on the structure and catalytic performance of ZnxCu1−xAl2O4 catalysts synthesized by the solution combustion method for the esterification reaction

A Zn_xCu_1−xAl₂O₄ catalyst was prepared via the microwave-assisted solution combustion method (MSC). This method presents a fast procedure for industrial scale catalyst preparation. The physicochemical properties of the fabricated catalyst were characterized using XRD, FTIR, BET, SEM and TEM analyses. The catalytic performance through the esterification reaction was examined under the following conditions: reaction temperature = 180 °C, catalyst concentration = 3% (w/w), molar ratio of oleic acid to methanol = 9 and reaction time = 6 h. XRD results showed that loading both zinc and copper oxides on alumina at a ratio of amounts that were nearly the same resulted in decreased crystalline size and well-dispersed copper-alumina and zinc-alumina crystals. Moreover, the mean pore diameter of the sample was increased by simultaneous loading of zinc and copper oxides on alumina that enhanced permeation of the reactants within pores and increased the interaction of the reactant with the catalyst active sites. The catalyst showed minimum tendency towards adsorbing moisture from air, which was attributed to it having less atoms on the surface through which binding with H₂O molecules takes place. The highest level of activity in the esterification reaction (96.9%) was obtained at the optimum ratio of the Zn:Cu molar ratio, identified to be 2:3. The sample particles ranged from 10 to 30 nm in size, without agglomeration.     

A thermodynamic study of the inclusion processes of α- andβ-cyclodextrins with the acid forms of methyl orange and methyl yellow

The effect of temperature on the UV-visible spectra of the acid forms of methyl orange and methyl yellow in the presence of - and-cyclodextrins was analysed in terms of 1 : 1 inclusion processes. Three inclusion processes were considered for each azo dye/cyclodextrin system. The processes are the apparent inclusion process, the ammonium inclusion process, and the azonium inclusion process. The values of H ⁰ and S ⁰ are reported for each process. The inclusion complexes of the ammonium tautomer are more stable than those of the azonium tautomer and -cyclodextrin inclusion complexes are more stable than those of-cyclodextrin. The inclusion processes resulted in a shift in the position of the tautomeric equilibrium of an azo dye. A significant color fading was observed in -cyclodextrin/methyl yellow solutions. No measurable changes in the absorbances were observed in the case of azo dye solutions containing -cyclodextrin.     

A validated high‑performance thin-layer chromatography method for the simultaneous determination of quercetin and gallic acid in Annona reticulata L.

JPC – Journal of Planar Chromatography – Modern TLC - A sensitive and reliable high-performance thin-layer chromatography (HPTLC) method has been developed to simultaneously estimate...     

L-cysteine-regulated in situ formation of Prussian blue/Turnbull’s blue nanoparticles as the colorimetric probe for the detection of copper ion

A fast, simple, sensitive, and selective colorimetric method for the detection of Cu²⁺ was developed using Prussian blue/Turnbull’s blue nanoparticles (PBNPs/TBNPs) as the probe. The colorimetric sensor is based on the following principle. Cu²⁺ can induce the aggregation of L-cysteine (L-cys) modified-PBNPs/TBNPs (L-cys-PBNPs/TBNPs), resulting in an obvious red shift of its maximum absorption peak. Thus, the concentration of Cu²⁺ can be determined based on the peak shift in the UV–Vis spectra. The optimal pH, concentration of L-cys, reaction temperature between L-cys-PBNPs/TBNPs and Cu²⁺, the formation time of L-cys-PBNPs/TBNPs, and the reaction time between L-cys-PBNPs/TBNPs and Cu²⁺ of the method were determined to be pH 4.5, 2.0 mM, 20 °C, 5.0 min, and 2.0 min, respectively. A good linearity for the colorimetric determination of Cu²⁺ at the range of 0.25–2.5 μM (R² = 0.986) was obtained, with a limit of detection (LOD) of 0.12 μM. Moreover, the negligible response of other metal ions demonstrates good selectivity and specificity of the sensor. In addition, the method was employed in the detection of Cu²⁺ in lake water samples, and the spiked recoveries are in the range of 96.7–106.6% with a relative standard deviation less than 7.4%. Therefore, the colorimetric method is applicable for Cu²⁺ detection in real water samples of high sensitivity and selectivity.     

Kinetics and mechanism of reactions of bis(biguanide)copper(II) ion with glycine and α-alanine in aqueous media

Summary The kinetics of the reaction of [Cu(bigH)₂]²⁺ (bigH = biguanide) with an excess of amino acid (LH), namely glycine or -alanine, in aqueous solution in the 7.6–9.0 pH range at different temperatures (30–40° C) have been followed by stopped-flow spectrophotometry. The ligand replacement process has been found to pass through intermediate formation of a ternary complex, [Cu(bigH)L]⁺ at the slower step, followed by rapid transformation into the binary complex, [CuL₂]. The overall ligand replacement process has a ligand dependent (k ₁) path which is first order with respect to the incoming ligand (L^-), and a ligand independent (k ₀) path. Under pseudo-first order conditions containing excess amino acid, the experimental observations conform to the rate law k _obs = k ₀ + k ₁ K _a[L]_T/([H⁼] + K _a), where [L]_T stands for the total concentration of amino acid and K _a gives the deprotonation constant of LH. The solvent assisted dissociation (i.e. k ₀ path) leads to a copper(II) mono-biguanide complex followed by rapid nucleophilic substitution; the k ₁ path is in agreement with an associative mechanism. The activation parameters (H , S ) for each step have been determined.     

A study of peptide—Peptide interactions using MALDI ion mobility o-TOF and ESI mass spectrometry

Matrix-assisted laser desorption ionization ion mobility coupled to orthogonal time-of-flight mass spectrometry (MALDI-IM-oTOF MS) is evaluated as a tool for studying non-covalent complex (NCX) formation between peptides. The NCX formed between dynorphin 1-7 and Mini Gastrin I is used as a model system for comparison to previous MALDI experiments (Woods, A. S.; Huestis, M. A. J. Am. Soc. Mass Spectrom. 2001, 12, 88-96). The dynorphin 1-7/Mini Gastrin I complex is stable after more than a ms drift time through the He filled mobility cell. Furthermore, the effects of solution pH on NCX ion signal intensity is measured both by MALDI-IM-MS analysis and by nanoelectrospray mass spectrometry. When compared to the previous MALDI study this work shows that all three techniques give similar results. In addition, fragmentation can be observed from of the non-covalent complex parent ion that occurs prior to TOF mass analysis but after mobility separation, thus providing NCX composition information.     

Chemical relevance of the copper(II)—l-carnosine system in aqueous solution: A thermodynamic and spectrophotometric study

The copper(II)—l-carnosine (L⁻) system has been re-investigated in aqueous solution, at I = 0.1 mol dm⁻¹, different temperatures (5⩽t⩽45°C) and with metal to ligand ratios ranging from 3:1 to 1:3. Both potentiometry and visible spectrophotometry were employed. From an overall consideration of all experiments, [CuLH]²⁺, [CuL]⁺, [CuLH₋₁]°, [Cu₂L₂H₋₂]° and [Cu₂LH₋₁]²⁺ were recognized as the species which provide the best interpretation of experimental data. The complex formation constants, determined at different temperatures, allowed us to obtain reliable values of ΔH° and good estimates of ΔC°_p. From visible spectrophotometric measurements, carried out at different pH and metal to ligand ratios, it was possible to calculate the electronic spectrum of each complex formed in solution. A structure is also proposed for each species, on the basis of thermodynamic and spectral results.     

Metal-amyloid-β peptide interactions: a preliminary investigation of molecular mechanisms for Alzheimer’s disease

Although humans have spent exactly 100 years combating Alzheimer’s disease (AD), the molecular mechanisms of AD remain unclear. Owing to the rapid growth of the oldest age groups of the popula-tion and the continuous increase of the incidence of AD, it has become one of the crucial problems to modern sciences. It would be impossible to prevent or reverse AD at the root without elucidating its molecular mechanisms. From the point of view of metal-amyloid-β peptide (Aβ) interactions, we review the molecular mechanisms of AD, mainly including Cu2 and Zn2 inducing the aggregation of Aβ, cata-lysing the production of active oxygen species from Aβ, as well as interacting with the ion-channel-like structures of Aβ. Moreover, the development of therapeutic drugs on the basis of metal-Aβ interactions is also briefly introduced. With the increasingly rapid progress of the molecular mechanisms of AD, we are now entering a new dawn that promises the delivery of revolutionary developments for the control of dementias.     

A critique of Weisberg’s view on the periodic table and some speculations on the nature of classifications

This article carefully analyzes a recent paper by Weisberg in which it is claimed that when Mendeleev discovered the periodic table he was not working as a modeler but instead as a theorist. I argue that Weisberg is mistaken in several respects and that the periodic table should be regarded as a classification, not as a theory. In the second part of the article an attempt is made to elevate the status of classifications by suggesting that they provide a form of ‘side-ways explanation’.