A P(V) platform for oligonucleotide synthesis.

The promise of gene-based therapies is being realized at an accelerated pace, with more than 155 active clinical trials and multiple U.S. Food and Drug Administration approvals for therapeutic oligonucleotides, by far most of which contain modified phosphate linkages. These unnatural linkages have desirable biological and physical properties but are often accessed with difficulty using phosphoramidite chemistry. We report a flexible and efficient [P(V)]­based platform that can install a wide variety of phosphate linkages at will into oligonucleotides. This approach uses readily accessible reagents and can install not only stereodefined or racemic thiophosphates but any combination of (S, R or rac)­PS with native phosphodiester (PO2) and phosphorodithioate (PS2) linkages into DNA and other modified nucleotide polymers. This platform easily accesses this diversity under a standardized coupling protocol with sustainably prepared, stable P(V) reagents.

CITU: A Peptide and Decarboxylative Coupling Reagent.

Tetrachloro-N-hydroxyphthalimide tetramethyluronium hexafluorophosphate (CITU) is disclosed as a convenient and economical reagent for both acylation and decarboxylative cross-coupling chemistries. Within the former set of reactions, CITU displays reactivity similar to that of common coupling reagents, but with increased safety and reduced cost. Within the latter, increased yields, more rapid conversion, and a simplified procedure are possible across a range of reported decarboxylative transformations.

Protective ligand shells for luminescent SiO2-coated alloyed semiconductor nanocrystals.

SiO2 encapsulation of alloyed CdSeZnS nanocrystals (NCs) shows differences in terms of optical properties and luminescence quantum yield, depending on the surface composition, size, and ligand content. In this work, emphasis has been placed on the fine control required to obtain luminescent SiO2 encapsulated NCs by studying the role of oleic acid (OA), stearic acid (SA), and dodecanethiol (DDT) ligands on the alloyed NCs. While the use of anchored DDT molecules is essential to preserve the optical properties, intercalated OA and SA play a critical role for SiO2 nucleation, as stated by (1)H NMR (including DOSY and NOESY) spectroscopy. These results emphasize the importance of surface chemistry in NCs; it is crucial to control their reactivity, and therefore their impact, in different applications, from optics to biomedicine.

Adiponectin promoter activator NP-1 reduces body weight and hepatic steatosis in high-fat diet-fed animals.

Enhancement of adiponectin level has been shown to have beneficial effects, including antiobesity, antidiabetic, and hepatoprotective effects. This evidence supports the therapeutic utility of adiponectin in complicated obesity. The present study characterized the in vivo effects of sustained adiponectin release by NP-1, a new class of thiazol derivative that increases adiponectin levels. Acute administration of NP-1 reduced feeding, increased plasma adiponectin, and improved insulin sensitivity without inducing malaise, as revealed by conditioned taste aversion studies. Short-term (7 days) treatment with NP-1 also reduced feeding and body weight gain and increased phosphorylation of AMPK in muscle, a main intracellular effector of adiponectin. NP-1 was also evaluated in diet-induced obesity, and adult male Wistar rats were fed two different types of diet: a standard high-carbohydrate/low-fat diet (SD) and a high-fat diet (HFD). Once obesity was established, animals were treated daily with NP-1 (5 mg/kg) for 14 consecutive days. Chronic NP-1 induced body weight loss and reduction of food intake and resulted in both a marked decrease in liver steatosis and an improvement of biochemical indexes of liver damage in HFD-fed rats. However, a marked induction of tolerance in adiponectin gene transcription and release was observed after chronic NP-1 with respect to the acute actions of this drug. The present results support the role of adiponectin signaling in diet-induced obesity and set in place a potential use of compounds able to induce adiponectin release for the treatment of obesity and nonalcoholic fatty liver, with the limits imposed by the induction of pharmacological tolerance.