Synthesis of Tris-hydroxymethyl-Based Nitrone Derivatives with Highly Reactive Nitronyl Carbon.

International audienceA novel series of α-phenyl-N-tert-butyl nitrone derivatives, bearing a hydrophobic chain on the aromatic ring and three hydroxyl functions on the tert-butyl group, was synthesized through a short and convenient synthetic route based on a one-pot reduction/condensation of tris(hydroxymethyl)nitromethane with a benzaldehyde derivative. Because of the presence of hydroxyl functions on the tert-butyl group, an intramolecular Forrester−Hepburn reaction leading to the formation of an oxazolidine-N-oxyl compound was observed by electron paramagnetic resonance (EPR). The mechanism of cyclization was further studied by computational methods showing that intramolecular hydrogen bonding and high positive charge on the nitronyl carbon could facilitate the nucleophilic addition of a hydroxyl group onto the nitronyl carbon. At high nitrone concentrations, a second paramagnetic species, very likely formed by intermolecular nucleophilic addition of two nitrone molecules, was also observed but to a lesser extent. In addition, theoretical data confirmed that the intramolecular reaction is much more favored than the intermolecular one. These nitrones were also found to efficiently trap carbon-centered radicals, but complex spectra were observed due to the presence of oxazolidine-N-oxyl derivatives. ■ INTRODUCTION Oxidative stress was defined as a disturbance in the prooxidant− antioxidant balance in favor of the former, leading to potential damage, and it has become clear that an overproduction of prooxidant molecules, also termed reactive oxygen and nitrogen species (ROS/RNS), is associated with several pathologies such as neurodegenerative diseases, cancers, and ischemia−reperfu-sion syndromes to name a few. 1 Consequently, any agent that can trap ROS/RNS to form more stable adducts, and as a result can alter the course of diseases progression, may be useful as a novel therapeutic approach. Of particular interest are nitrone spin-traps, which undergo addition reaction with free radicals, making them a popular analytical reagent for the identification of short-lived radicals using electron paramagnetic resonance (EPR) spectroscopy. 2,

<i>mimic</i>INT: a workflow for microbe-host protein interaction inference

The increasing incidence of emerging infectious diseases is posing serious global threats. Therefore, there is a clear need for developing computational methods that can assist and speed-up experimental research to better characterize the molecular mechanisms of microbial infections. In this context, we developed mimicINT, a freely available computational workflow for large-scale protein-protein interaction inference between microbe and human by detecting putative molecular mimicry elements that can mediate the interaction with host proteins: short linear motifs (SLiMs) and hostlike globular domains. mimicINT exploits these putative elements to infer the interaction with human proteins by using known templates of domain-domain and SLiM-domain interaction templates. mimicINT provides (i) robust Monte-Carlo simulations to assess the statistical significance of SLiM detection which suffers from

Antibodies enhance the infection of phorbol-ester-differentiated human monocyte-like cells with coxsackievirus B4

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High-Density Lipoprotein-Associated miR-223 Is Altered after Diet-Induced Weight Loss in Overweight and Obese Males.

microRNAs (miRNAs) are small, endogenous non-coding RNAs that regulate metabolic processes, including obesity. The levels of circulating miRNAs are affected by metabolic changes in obesity, as well as in diet-induced weight loss. Circulating miRNAs are transported by high-density lipoproteins (HDL) but the regulation of HDL-associated miRNAs after diet-induced weight loss has not been studied. We aim to determine if HDL-associated miR-16, miR-17, miR-126, miR-222 and miR-223 levels are altered by diet-induced weight loss in overweight and obese males.HDL were isolated from 47 subjects following 12 weeks weight loss comparing a high protein diet (HP, 30% of energy) with a normal protein diet (NP, 20% of energy). HDL-associated miRNAs (miR-16, miR-17, miR-126, miR-222 and miR-223) at baseline and after 12 weeks of weight loss were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. Serum concentrations of human HDL constituents were measured immunoturbidometrically or enzymatically.miR-16, miR-17, miR-126, miR-222 and miR-223 were present on HDL from overweight and obese subjects at baseline and after 12 weeks of the HP and NP weight loss diets. The HP diet induced a significant decrease in HDL-associated miR-223 levels (p = 0.015), which positively correlated with changes in body weight (r = 0.488, p = 0.032). Changes in miR-223 levels were not associated to changes in HDL composition or size.HDL-associated miR-223 levels are significantly decreased after HP diet-induced weight loss in overweight and obese males. This is the first study reporting changes in HDL-associated miRNA levels with diet-induced weight loss

Synthesis of Tris-hydroxymethyl-Based Nitrone Derivatives with Highly Reactive Nitronyl Carbon

A novel series of α-phenyl-<i>N</i>-<i>tert</i>-butyl nitrone derivatives, bearing a hydrophobic chain on the aromatic ring and three hydroxyl functions on the <i>tert</i>-butyl group, was synthesized through a short and convenient synthetic route based on a one-pot reduction/condensation of tris­(hydroxymethyl)­nitromethane with a benzaldehyde derivative. Because of the presence of hydroxyl functions on the <i>tert</i>-butyl group, an intramolecular Forrester–Hepburn reaction leading to the formation of an oxazolidine-<i>N</i>-oxyl compound was observed by electron paramagnetic resonance (EPR). The mechanism of cyclization was further studied by computational methods showing that intramolecular hydrogen bonding and high positive charge on the nitronyl carbon could facilitate the nucleophilic addition of a hydroxyl group onto the nitronyl carbon. At high nitrone concentrations, a second paramagnetic species, very likely formed by intermolecular nucleophilic addition of two nitrone molecules, was also observed but to a lesser extent. In addition, theoretical data confirmed that the intramolecular reaction is much more favored than the intermolecular one. These nitrones were also found to efficiently trap carbon-centered radicals, but complex spectra were observed due to the presence of oxazolidine-<i>N</i>-oxyl derivatives

High-Density Lipoprotein-Associated miR-223 Is Altered after Diet-Induced Weight Loss in Overweight and Obese Males.

microRNAs (miRNAs) are small, endogenous non-coding RNAs that regulate metabolic processes, including obesity. The levels of circulating miRNAs are affected by metabolic changes in obesity, as well as in diet-induced weight loss. Circulating miRNAs are transported by high-density lipoproteins (HDL) but the regulation of HDL-associated miRNAs after diet-induced weight loss has not been studied. We aim to determine if HDL-associated miR-16, miR-17, miR-126, miR-222 and miR-223 levels are altered by diet-induced weight loss in overweight and obese males.HDL were isolated from 47 subjects following 12 weeks weight loss comparing a high protein diet (HP, 30% of energy) with a normal protein diet (NP, 20% of energy). HDL-associated miRNAs (miR-16, miR-17, miR-126, miR-222 and miR-223) at baseline and after 12 weeks of weight loss were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. Serum concentrations of human HDL constituents were measured immunoturbidometrically or enzymatically.miR-16, miR-17, miR-126, miR-222 and miR-223 were present on HDL from overweight and obese subjects at baseline and after 12 weeks of the HP and NP weight loss diets. The HP diet induced a significant decrease in HDL-associated miR-223 levels (p = 0.015), which positively correlated with changes in body weight (r = 0.488, p = 0.032). Changes in miR-223 levels were not associated to changes in HDL composition or size.HDL-associated miR-223 levels are significantly decreased after HP diet-induced weight loss in overweight and obese males. This is the first study reporting changes in HDL-associated miRNA levels with diet-induced weight loss

Reactivities of Substituted α-Phenyl- \textitN - \textittert -butyl Nitrones

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