1<i>H</i>‑Azepine-2-oxo-5-amino-5-carboxylic Acid: A 3₁₀ Helix Inducer and an Effective Tool for Functionalized Gold Nanoparticles

A new α,α-disubstituted constrained glutamine analogue has been designed to decorate gold nanoparticles and to induce a 3₁₀-helix when inserted in peptides. Using an efficient “one-pot” asymmetric Schmidt reaction between 4-disubstituted-cyclohexanone and hydroxyalkylazides, 1<i>H</i>-azepine-2-oxo-5-amino-5-carboxylic acid was prepared. The main (<i>R</i>) isomer was inserted at the N-terminus in a very short peptide sequence (i.e., PhCO-(<i>R</i>)-Oxo-Azn-l-Ala-Aib-l-AlaNHMe) and a stable 3₁₀-helix conformation was obtained, as verified by both NMR experiments and molecular dynamics (MD) simulations. Finally, the presence of the hydroxyl chain at the nitrogen atom of the ring allowed for the preparation of covered chiral gold nanoparticles

2‑Amino-3-(phenylsulfanyl)norbornane-2-carboxylate: An Appealing Scaffold for the Design of Rac1–Tiam1 Protein–Protein Interaction Inhibitors

The use of the 2-amino-3-(phenylsulfanyl)­norbornane-2-carboxylate scaffold has been exploited for the de novo design of potent Rac1 inhibitors acting as modulators of the protein–protein interaction between Rac1 and Tiam1. A series of compounds differing in regio- and stereochemistry has been prepared by way of a multistep synthesis based on cycloaddition reactions and Pd chemistry. Pharmacological analyses showed that all the prepared compounds were active and selective for Rac1, and the most effective compound <b>13</b> was capable of inhibiting smooth muscle cell migration. The synthesis of this derivative was successfully scaled up to 1 g

Interventional Studies on dementia in Europe (Available: www.clinicaltrials.gov; accessed 2010 May 3).

<p>Interventional Studies on dementia in Europe (Available: <a href="http://www.clinicaltrials.gov" target="_blank">www.clinicaltrials.gov</a>; accessed 2010 May 3).</p

Patients applying and not applying to appoint a legal proxy and the time required for appointment.

<p>Patients applying and not applying to appoint a legal proxy and the time required for appointment.</p

MediaChrom: Discovering a Class of Pyrimidoindolone-Based Polarity-Sensitive Dyes

A small library of six polarity-sensitive fluorescent dyes, nicknamed MediaChrom, was prepared. This class of dyes is characterized by a pyrimidoindolone core fitted out with a conjugated push–pull system and a carboxy linker for a conceivable coupling with biomolecules. The optimized eight-step synthetic strategy involves a highly chemo- and regioselective gold-catalyzed cycloisomerization reaction. The photophysical properties of MediaChrom dyes have been evaluated in-depth. In particular, the MediaChrom bearing a diethylamino as an electron-donating group and a trifluoromethyl as an electron-withdrawing group displays the most interesting and advantageous spectroscopic features (e.g., absorption and emission in the visible range and a good quantum yield). Promising results in terms of sensitivity have been obtained in vitro on this dye as a membrane/lipophilic probe and as a peptide fluorescent label

Baseline patient characteristics.

<p>MMSE: Mini Mental State Examination.</p><p>ADL: Activity of Daily Living.</p><p>IADL: Instrumental Activity of Daily Living.</p><p>AChE-Is: Cholinesterase Inhibitors.</p

Predictive variables of appointment: results of the logistic regression analysis.

<p>Predictive variables of appointment: results of the logistic regression analysis.</p

Baseline characteristics and comorbidities in the whole sample, in stable MCI at follow up and in MCI progressed to dementia.

<p>Baseline characteristics and comorbidities in the whole sample, in stable MCI at follow up and in MCI progressed to dementia.</p

Progression to dementia of MCI subjects divided into three categories of weight change.

<p>Progression to dementia of MCI subjects divided into three categories of weight change.</p

Relative risk of progression from MCI to dementia and Alzheimer's disease in relation to weight change: Cox regression model adjusted for the potential confounding variables in 102 subjects.

<p>Relative risk of progression from MCI to dementia and Alzheimer's disease in relation to weight change: Cox regression model adjusted for the potential confounding variables in 102 subjects.</p