Introduction of C-Sulfonate Groups into Disaccharide Derivatives

To prepare C-sulfonate derivatives of disaccharides two different strategies were followed. Thus 6- and 6′-C-sulfocellobiosides 4 and 10–12 were prepared starting from a suitably protected cellobioside. The 6′-C-sulfoaminocellobioside 18 was prepared by construction of the molecule through a glycosylation reaction. In both cases, the synthetic pathway involves regioselective tosylation, introduction of a sulfur atom by nucleophilic displacement with potassium thioacetate and oxidation with hydrogen peroxide.     

Mixing method influence on compatibility and polymorphism studies by DSC and statistical analysis

Most of the pharmaceutical products are formulated as solid dosage form, which may present drug–excipient interactions that lead to changes in the chemical nature of the drug, such as solubility and bioavailability and may compromise its safety and effectiveness. Differential scanning calorimetry (DSC) is a widely used method for the rapid evaluation of the drug-excipient compatibility and the stability of the mixture formed; however, there is no consensus on the preparation methods of the drug–excipient mixtures. The aim of this study was to investigate the influence of the mixing method on the drug–excipient compatibility studies by means of DSC analysis, using tenofovir disoproxil fumarate as a drug model. Statistical analysis revealed significant differences in the heat of fusion of the drug in the mixtures prepared by several mixing methods. Vortex Mixer with a Pop-Off Cup used for 3 min proved to be very satisfactory for these studies. A polymorphic transition was observed in the mixture prepared with the mortar and pestle. Therefore, this method should be avoided since it may induce errors in the interpretation of DSC results. In this way, the mixing method used to prepare a mixture for studies of interactions between the API and the excipients in a pharmaceutical formulation has a great influence on the results and it must be chosen carefully.     

An effective and rapid determination by MALDI/TOF/TOF of methionine sulphoxide content of ApoA‐I in type 2 diabetic patients

Increased oxidation of low density lipoprotein (LDL) is characteristic of atherosclerosis. In this frame, high density lipoproteins (HDL) play an important role, being able to remove lipid peroxides (LPOs) and cholesterol from oxidized LDL, so exhibiting a protective role against atherosclerosis. A wide range of reactive compounds lead to the oxidation of methionine (Met) residues with the formation of methionine sulphoxide (MetO) in apolipoprotein A‐I (ApoA‐I). Consequently, the determination of MetO level can give both an evaluation of oxidative stress and the reduced capability of ApoA‐I in LPOs and cholesterol transport. For these reasons, the development of analytical methods able to determine the MetO level is surely of interest, and we report here the results obtained by MALDI mass spectrometry. Copyright © 2013 John Wiley & Sons, Ltd.     

Exploring the Phase-Selective,Green, Hydrothermal Synthesis of Upconverting Doped Sodium Yttrium Fluoride: Effects of Temperature,Time, and Precursors

The aim of this work was i) to develop a hydrothermal, low-temperature synthesis protocol affording the upconverting hexagonal phase NaYF₄ with suitable dopants while adhering to the “green chemistry” standards and ii) to explore the effect that different parameters have on the products. In optimizing the synthesis protocol, short reaction times and low temperatures (below 150 °C) were considered. Yb³⁺ and Er³⁺ ions were chosen as dopants for the NaYF₄ material. Within the context of the second goal, parameters including nature of the precursors, treatment temperature, and treatment time were investigated to afford a pure hexagonal crystalline phase, both in the doped and undoped materials. To fully explore the synthesis results, the prepared materials were characterized from a structural (XRD), compositional (XPS, ICP-MS), and morphological (SEM) point of view. The upconverting properties of the compounds were confirmed by photoluminescence measurements.     

Enantioselective Synthesis of α-Thiocarboxylic Acids by Nitrilase Biocatalysed Dynamic Kinetic Resolution of α-Thionitriles

The enantioselective synthesis of α-thiocarboxylic acids by biocatalytic dynamic kinetic resolution (DKR) of nitrile precursors exploiting nitrilase enzymes is described. A panel of 35 nitrilase biocatalysts were screened and enzymes Nit27 and Nit34 were found to catalyse the DKR of racemic α-thionitriles under mild conditions, affording the corresponding carboxylic acids with high conversions and good-to-excellent ee. The ammonia produced in situ during the biocatalytic transformation favours the racemization of the nitrile enantiomers and, in turn, the DKR without the need of any external additive base.     

The Glycolytic Pathway as a Target for Novel Onco-Immunology Therapies in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal forms of human cancer, characterized by unrestrained progression, invasiveness and treatment resistance. To date, there are limited curative options, with surgical resection as the only effective strategy, hence the urgent need to discover novel therapies. A platform of onco-immunology targets is represented by molecules that play a role in the reprogrammed cellular metabolism as one hallmark of cancer. Due to the hypoxic tumor microenvironment (TME), PDA cells display an altered glucose metabolism—resulting in its increased uptake—and a higher glycolytic rate, which leads to lactate accumulation and them acting as fuel for cancer cells. The consequent acidification of the TME results in immunosuppression, which impairs the antitumor immunity. This review analyzes the genetic background and the emerging glycolytic enzymes that are involved in tumor progression, development and metastasis, and how this represents feasible therapeutic targets to counteract PDA. In particular, as the overexpressed or mutated glycolytic enzymes stimulate both humoral and cellular immune responses, we will discuss their possible exploitation as immunological targets in anti-PDA therapeutic strategies.