Live Monitoring of Cargo Release From Peptide‐Based Hybrid Nanocapsules Induced by Enzyme Cleavage

The miniemulsion process is used as a new route for the preparation of enzyme‐responsive nanocapsules with payload‐release properties. Peptide‐based hybrid nanocapsules are prepared via interfacial polyaddition containing a water‐soluble dye that is efficiently encapsulated inside. The influence of the synthetic parameters as the functionality of the peptide and the nature of the dispersed phase on the structure of the nanocapsules were investigated. After redispersion in water, the enzymatic cleavage of the peptide sequence and the release of the fluorescent dye are both monitored in real time. This is evidenced because of the quenching FRET system framing the recognition site in the peptide sequence, and the fluorescence recovery of the self‐quenched encapsulated dye respectively.     

An online nano‐LC‐ESI‐FTICR‐MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid

Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low‐energy collision‐induced dissociation tandem mass spectrometry (MS/MS), mainly long b‐fragments are observed, limiting the possibility to determine variations such as amino acid variants or post‐translational modifications (PTMs) within the N‐terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann–Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O‐glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top‐down MS‐based method. Copyright © 2012 John Wiley & Sons, Ltd.     

A numerical algorithm for nonlinear parabolic equations with highly oscillating coefficients

A numerical algorithm is constructed for the solution to a class of nonlinear parabolic operators in the case of homogenization. We consider parabolic operators of the form d/dt + A_ϵ, where A_ϵ is monotone. More precisely, we consider the case when A_ϵu=−div (a(x/ϵ, e/ϵ^k) |Du|^p−2Du), where p≥2 and k>0. © 1996 John Wiley & Sons, Inc.     

Homogeneous Reforming of Aqueous Ethylene Glycol to Glycolic Acid and Pure Hydrogen Catalyzed by Pincer-Ruthenium Complexes Capable of Metal–Ligand Cooperation

Glycolic acid is a useful and important α-hydroxy acid that has broad applications. Herein, the homogeneous ruthenium catalyzed reforming of aqueous ethylene glycol to generate glycolic acid as well as pure hydrogen gas, without concomitant CO₂ emission, is reported. This approach provides a clean and sustainable direction to glycolic acid and hydrogen, based on inexpensive, readily available, and renewable ethylene glycol using 0.5 mol % of catalyst. In-depth mechanistic experimental and computational studies highlight key aspects of the PNNH-ligand framework involved in this transformation.     

A Simple Nickel Catalyst Enabling an E-Selective Alkyne Semihydrogenation

Stereoselective alkyne semihydrogenations are attractive approaches to alkenes, which are key building blocks for synthesis. With regards to the most atom-economic reducing agent dihydrogen (H₂), only few catalysts for the challenging E-selective alkyne semihydrogenation have been disclosed, each with a unique substrate scope profile. Here, we show that a commercially available nickel catalyst facilitates the E-selective alkyne semihydrogenation of a wide variety of substituted internal alkynes. This results in a simple and broadly applicable overall protocol to stereoselectively access E-alkenes employing H₂, which could serve as a general method for synthesis.     

On two-scale convergence and related sequential compactness topics

A general concept of two-scale convergence is introduced and two-scale compactness theorems are stated and proved for some classes of sequences of bounded functions in L ²(Ω) involving no periodicity assumptions. Further, the relation to the classical notion of compensated compactness and the recent concepts of two-scale compensated compactness and unfolding is discussed and a defect measure for two-scale convergence is introduced.     

Thermoluminescence of YAG:Nd crystals coloured with x-rays

The spectral distribution of the thermoluminescence (TL) of YAG:Nd crystals coloured by x-ray irradiation at room temperature (RT) and at 80 K has been investigated. The spectral distribution of TL in the uv-, visible and near ir ranges shows that the energy transfer by bound exciton states (BES) to the RE³⁺ ions (Nd³⁺ and Tb³⁺) decreases with increasing temperature. The TL spectrum in the uv range is ascribed to the hole defect centers. Diminution of the energy transferred by the BES to the Nd³⁺ and Tb³⁺ ions is the direct cause for the occurrence of the group of lines ascribed to the Nd³⁺ ions in TL observed at LT, whereas at RT and higher only the groups of Tb lines are observed.     

Synthetic applications of 3‐(cyanoacetyl)indoles and related compounds

Various synthetic applications of 3‐(cyanoacetyl)indoles, as well as syntheses of some related indoles, have been investigated. Diethyl 2‐(1H‐indol‐3‐yl)‐2‐oxoethylphosphonate and a methyl derivative thereof have been prepared in one step from indole. Moreover, it was demonstrated that 3‐(cyanoacetyl)indoles are useful starting materials for the preparation of for example 3‐(1H‐indol‐3‐yl)‐3‐oxopropanamides, 3‐heteroarylindoles or 3‐heteroaroylindoles.     

Production of milligram quantities of affinity tagged-proteins using automated multistep chromatographic purification

A new chromatography system, AKTAxpress (GE Healthcare, Amersham Biosciences, Uppsala, Sweden) has been designed to meet the demand for high-throughput purification of proteins in structural genomics and drug discovery. The system offers a number of automated multistep purification protocols for affinity-tagged proteins. All protocols start with affinity chromatography followed by combinations of desalting, ion exchange chromatography and gel filtration. As an option, tag removal can be included in the purification protocols. Up to 16 proteins can be purified per day and the yield can be as high as 50 mg of each protein at > 90% purity. To highlight the versatility of the system, this paper presents several case studies; purifications of hexahistidine- and glutathione S-transferase-tagged proteins using different protocols, automated on-column tag cleavage and optimization studies for a hexahistidine-tagged kinase.     

Interaction of Metal Oxido Compounds with B(C6F5)3

Lewis acid–base pair chemistry has been placed on a new level with the discovery that adduct formation between an electron donor (Lewis base) and acceptor (Lewis acid) can be inhibited by the introduction of steric demand, thus preserving the reactivity of both Lewis centers, resulting in highly unusual chemistry. Some of these highly versatile frustrated Lewis pairs (FLP) are capable of splitting a variety of small molecules, such as dihydrogen, in a heterolytic and even catalytic manner. This is in sharp contrast to classical reactions where the inert substrate must be activated by a metal-based catalyst. Very recently, research has emerged combining the two concepts, namely the formation of FLPs in which a metal compound represents the Lewis base, allowing for novel chemistry by using the heterolytic splitting power of both together with the redox reactivity of the metal. Such reactivity is not restricted to the metal center itself being a Lewis acid or base, also ancillary ligands can be used as part of the Lewis pair, still with the benefit of the redox-active metal center nearby. This Minireview is designed to highlight the novel reactions arising from the combination of metal oxido transition-metal or rare-earth-metal compounds with the Lewis acid B(C₆F₅)₃. It covers a wide area of chemistry including small molecule activation, hydrogenation and hydrosilylation catalysis, and olefin metathesis, substantiating the broad influence of the novel concept. Future goals of this young and exciting area are briefly discussed.