Designed helical peptides inhibit an intramembrane protease

gamma-Secretase cleaves the transmembrane domain of the amyloid precursor protein, a process implicated in the pathogenesis of Alzheimer's disease, and this enzyme is a founding member of an emerging class of intramembrane proteases. Modeling and mutagenesis suggest a helical conformation for the substrate transmembrane domain upon initial interaction with the protease. Moreover, biochemical evidence supports the presence of an initial docking site for substrate on gamma-secretase that is distinct from the active site, a property predicted to be generally true of intramembrane proteases. Here we show that short peptides designed to adopt a helical conformation in solution are inhibitors of gamma-secretase in both cells and enzyme preparations. Helical peptides with all d-amino acids are the most potent inhibitors and represent potential therapeutic leads. Subtle modifications that disrupt helicity also substantially reduce potency, suggesting that this conformation is critical for effective inhibition. Fluorescence lifetime imaging in intact cells demonstrates that helical peptides disrupt binding between substrate and protease, whereas an active site-directed inhibitor does not. These findings are consistent with helical peptides interacting with the initial substrate docking site of gamma-secretase, suggesting a general strategy for the development of potent and specific inhibitors of intramembrane proteases.     

On the Role of Symmetry in Vibrational Strong Coupling: The Case of Charge‐Transfer Complexation

It is well known that symmetry plays a key role in chemical reactivity. Here we explore its role in vibrational strong coupling (VSC) for a charge‐transfer (CT) complexation reaction. By studying the trimethylated‐benzene–I₂ CT complex, we find that VSC induces large changes in the equilibrium constant K_DA of the CT complex, reflecting modifications in the ΔG° value of the reaction. Furthermore, by tuning the microfluidic cavity modes to the different IR vibrations of the trimethylated benzene, ΔG° either increases or decreases depending only on the symmetry of the normal mode that is coupled. This result reveals the critical role of symmetry in VSC and, in turn, provides an explanation for why the magnitude of chemical changes induced by VSC are much greater than the Rabi splitting, that is, the energy perturbation caused by VSC. These findings further confirm that VSC is powerful and versatile tool for the molecular sciences.     

Two novel sesterterpene hydroxyquinols from the sponge microcionatoxistyla

The structures of two unique sesterpenes, toxislylide A and B, have been deduced by chemical, spectral, and x-ray crystallographic studies. They are components of the sponge $\text{Microciona}$$\text{toxistyla}$.     

Polarization tomography of metallic nanohole arrays

We report polarization tomography experiments on metallic nanohole arrays with square and hexagonal symmetry. As a main result we find that a fully polarized input beam is partly depolarized after transmission through a nanohole array. This loss of polarization coherence is found to be anisotropic; i.e., it depends on the polarization state of the input beam. The depolarization is ascribed to a combination of two factors: (i) the nonlocal response of the array as a result of surface-plasmon propagation and (ii) the non-plane-wave nature of a practical input beam.     

A Practical Catalytic Procedure for Oxidation of Alcohols Into Aldehydes or Ketones with RuCl3/Water and Ca(OCl)2 or NaIO4

Ruthenium complexes catalyze the oxidation of alcohols to the corresponding ketones or aldehydes when Ca(OCl)₂ or NaIO₄ are used as oxygen donors in the presence of water (5–10 equiv.). The reactions take place at room temperature affording products in yields of 45–80%.     

XPS analysis of bio‐organic systems

A survey of the literature is made for the XPS analysis of food products (mainly spray‐dried powders, which reveal a considerable surface enrichment in lipids) and of microorganisms and related systems (extracellular polymer substances and biofilms). This survey is used as a background for discussions and recommendations regarding methodology. Sample preparation methods reviewed are freeze drying, analysis of frozen hydrated specimens and adsorption of surface‐active biocompounds on model substrates. Peak decomposition is a way to increase the wealth of information provided by the XPS spectra. It should be performed after a check that sample charge stabilization is satisfactory. Moreover, ensuring the precision needed to make comparisons within sets of samples may involve a trade‐off between imposing constraints and generating information. The examination of correlations between spectral data in the light of chemical guidelines is useful to validate or improve peak decomposition and component assignment, and may also upgrade the chemical information regarding speciation. Further upgrading may be achieved by expressing marker XPS data in terms of concentrations of compounds of interest. Different methods of computation are discussed, providing a composition in terms of ingredients, classes of biochemical compounds, or various organic and inorganic compounds. As an alternative or complement to this deterministic approach, multivariate analysis of suitable spectral windows provides spectral components, which may be used for comparing samples, and which may have a direct chemical relevance or be used to identify features of interest. Copyright © 2011 John Wiley & Sons, Ltd.     

Allylic alkylations catalyzed by the couple palladium complexes-alumina

Using both palladium complexes and alumina, nucleophilic substitution of allyl acetate by various nucleophiles (pKa = 5–13) are realized with good yields at room temperature without preformation of the corresponding carbanions.     

Synthesis of (+) dictyopterene a constituent of marine brown algae and (+) dictyopterene C′ by chirality transfer of optically active allylic benzoate with palladium (O) catalyst.

The first enantioselective syntheses of (+) dictyopterene A $\text{1}$ and (+)dictyopterene C′ were reported. The key reaction was based on palladium promoted cyclisation of chiral allylic benzoate $\text{5}$ with transfer of chirality (anti attack of the palladium with respect to the leaving group) to give optically active vinylcyclopropane $\text{7}$ with (R) configuration which contains proper functionality for further elaboration into $\text{1}$ and $\text{3}$     

Starfish saponins,part 8. Structure of nodososide,a novel type of steroidal glycoside from the starfish protoreaster nodosus

A novel steroidal glycoside has been isolated from the starfish Protoreaster nodosus. The structure includes a 3β,5α,6β,8β,15α,24ξ-hexahydroxysteroidal moiety and a sugar moiety [2-0-methyl-β-D-xylopyranosyl-(1 → 2)-α-L-arabinofuranosyl] which is glycosidically attached at C-24 of the aglycone.