Double Orthogonal Click Reactions for the Development of Antimicrobial Peptide Nanotubes

A new class of amphipathic cyclic peptides, which assemble in bacteria membranes to form polymeric supramolecular nanotubes giving them antimicrobial properties, is described. The method is based on the use of two orthogonal clickable transformations to incorporate different hydrophobic or hydrophilic moieties in a simple, regioselective, and divergent manner. The resulting cationic amphipathic cyclic peptides described in this article exhibit strong antimicrobial properties with a broad therapeutic window. Our studies suggest that the active form is the nanotube resulted from the parallel stacking of the cyclic peptide precursors. Several techniques, CD, FTIR, fluorescence, and STEM, among others, confirm the nanotube formation.     

Design and Synthesis of New Withaferin A Inspired Hedgehog Pathway Inhibitors

Withanolides constitute a well-known family of plant-based alkaloids characterised by widespread biological properties, including the ability of interfering with Hedgehog (Hh) signalling pathway. Following our interest in natural products and in anticancer compounds, we report here the synthesis of a new class of Hh signalling pathway inhibitors, inspired by withaferin A, the first isolated member of withanolides. The decoration of our scaffolds was rationally supported by in silico studies, while functional evaluation revealed promising candidates, confirming once again the importance of natural products as inspiration source for the discovery of novel bioactive compounds. A stereoselective approach, based on Brown chemistry, allowed the obtainment and the functional evaluation of the enantiopure hit compounds.     

Hair analysis as a new tool to monitor adherence to long-term therapy to statins

Statins are cholesterol-lowering medications which are widely prescribed as first-line treatment for hyperlipidemia, against high blood cholesterol aimed at reducing the risk of atherosclerotic diseases. Notwithstanding their undoubted efficacy, the needed long-term treatment with these drugs is characterized by a high percentage of dropout. Consequently, an effective tool to verify the patients’ compliance to statin therapy is needed. In this context, the analysis for drugs and drug metabolites in the hair may represent an almost ideal tool because, according to a sound body of forensic toxicological literature, concentrations in the hair matrix reflect the chronic intake of drugs and pharmaceuticals. In this light, in the present study, a novel, specific and sensitive ultra-performance liquid chromatography–tandem mass spectrometry method has been developed to determine six statins and their metabolites (namely atorvastatin, (p)α-OH-atorvastatin-lactone, (o)α-OH-atorvastatin-lactone, rosuvastatin, N-desmethyl rosuvastatin and pravastatin) in human hair. After optimization, the method was successfully validated in terms of selectivity, linearity, sensitivity, precision, accuracy, stability and matrix effect. Moreover, the practical applicability of this method for verifying adherence to statin therapy was assessed by testing samples of hair collected from subjects under long-term therapy with statins.     

Orange Peel Biomass-derived Carbon Supported Cu Electrocatalysts Active in the CO2-Reduction to Formic Acid

We report a green, wet chemistry approach towards the production of C-supported Cu electrocatalysts active in the CO₂ reduction to formic acid. We use citrus peels as a C support precursor and as a source of reducing agents for the Cu cations. We show that orange peel is a suitable starting material compared to lemon peel for the one-pot hydrothermal synthesis of Cu nanostructures affording better Cu dispersion as well as productivity and selectivity towards formic acid. We rationalize this finding in terms of the beneficial chemical composition of the orange peel, which favors both the reduction of the Cu precursor as well as the carbon matrix. This work demonstrates new viable opportunities for the reuse of citrus waste on a rational basis.     

Entangling macroscopic oscillators exploiting radiation pressure

It is shown that radiation pressure can be profitably used to entangle macroscopic oscillators like movable mirrors, using present technology. We prove a new sufficient criterion for entanglement and show that the achievable entanglement is robust against thermal noise. Its signature can be revealed using common optomechanical readout apparatus.     

The energy-scale-dependent composite operator method for the single-impurity Anderson model

The recently developed energy-scale-dependent Composite Operator Method is applied to the single-impurity Anderson model. A fully self-consistent solution is given and analyzed. At very low temperatures, the density of states presents, on the top of the high-energy background, a Kondo-like peak whose parameter dependence is discussed in detail. The proposed method reproduces the exact results known in the literature with very low numerical effort and it is applicable for arbitrary values of the external parameters.Received: 24 September 2003, Published online: 9 April 2004PACS: 75.50.Ee Antiferromagnetics - 75.30.Et Exchange and superexchange interactions - 75.25. + z Spin arrangements in magnetically ordered materials (including neutron and spin-polarized electron studies, synchrotron-source X-ray scattering, etc.) - 75.50.-y Studies of specific magnetic materials     

Hot dense capsule-implosion cores produced by Z-pinch dynamic Hohlraum radiation

Hot dense capsule implosions driven by Z-pinch x rays have been measured using a approximately 220 eV dynamic Hohlraum to implode 1.7-2.1 mm diameter gas-filled CH capsules. The capsules absorbed up to approximately 20 kJ of x rays. Argon tracer atom spectra were used to measure the T(e) approximately 1 keV electron temperature and the n(e) approximately 1-4 x 10(23) cm(-3) electron density. Spectra from multiple directions provide core symmetry estimates. Computer simulations agree well with the peak emission values of T(e), n(e), and symmetry, indicating reasonable understanding of the Hohlraum and implosion physics.     

A solid-phase approach towards the development of 3-aza-6,8-dioxabicyclo[3.2.1]octane scaffolds

The development of new strategies for solid-phase synthesis of 3-aza-6,8-dioxabicyclo[3.2.1]octane scaffolds, named BTKa, is described. The preparation was made possible by the combination of three components: amines, alpha-halo-acetophenones, and sugar or tartaric acid derivatives. By anchoring each of the three components it was possible to synthesize BTKa compounds either as amino alcohols or amido esters. The compatibility of the protocols with different classes of amines and substituted alpha-halo-acetophenones was demonstrated.     

Abelian fourfold of Mumford-type and Kuga-Satake varieties

Let X be a complex abelian fourfold of Mumford-type and let V = H¹(X, ). The complex Mumford-Tate group of X is isogenous to SL(2)³. We recover information about the Hodge structure of X using representations of the Lie algebras (2)³ and (8) acting on V . Using these techniques we show that there is a Kuga-Satake variety A associated to X in such a way that A is isogenous to X³².