Solid-Phase Synthesis and In-Silico Analysis of Iron-Binding Catecholato Chelators

Siderophores are iron-complexing compounds synthesized by bacteria and fungi. They are low molecular weight compounds (500-1500 Daltons) possessing high affinity for iron(III). Since 1970 a large number of siderophores have been characterized, the majority using hydroxamate or catecholate as functional groups. The biosynthesis of siderophores is typically regulated by the iron levels of the environment where the organism is located. Because of their exclusive affinity and specificity for iron(III), natural siderophores and their synthetic derivatives have been exploited in the treatment of human iron-overload diseases, as both diagnostic and therapeutic agents. Here, solid-phase approach for the preparation of hexadentate, peptide-based tricatecholato containing peptides is described. The versatility of the synthetic method allows for the design of a common scaffolding structure whereby diverse ligands can be conjugated. With so many possibilities, a computational approach has been developed which will facilitate the identification of those peptides which are capable of providing a high affinity iron(III) binding site. This study reports an integrated computational/synthetic approach towards a rational development of peptide-based siderophores

Dual-Targeted Hyaluronic Acid/Albumin Micelle-Like Nanoparticles for the Vectorization of Doxorubicin

Drug targeting of tumor cells is one of the great challenges in cancer therapy; nanoparticles based on natural polymers represent valuable tools to achieve this aim. The ability to respond to environmental signals from the pathological site (e.g., altered redox potential), together with the specific interaction with membrane receptors overexpressed on cancer cells membrane (e.g., CD44 receptors), represent the main features of actively targeted nanoparticles. In this work, redox-responsive micelle-like nanoparticles were prepared by self-assembling of a hyaluronic acid–human serum albumin conjugate containing cystamine moieties acting as a functional spacer. The conjugation procedure consisted of a reductive amination step of hyaluronic acid followed by condensation with albumin. After self-assembling, nanoparticles with a mean size of 70 nm and able to be destabilized in reducing media were obtained. Doxorubicin-loaded nanoparticles modulated drug release rate in response to different redox conditions. Finally, the viability and uptake experiments on healthy (BALB-3T3) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a drug vector in cancer therapyL.D.-G. acknowledges Consellería de Cultura, Educación e Ordenación Universitaria for a postdoctoral fellowship (Xunta de Galicia, Spain; ED481B 2017/063)S

Evaluation of the Shelf life of Ready-to-Eat Fresh Bamboo Sprouts (<i>Phyllostachys edulis</i>) Packaged in a Modified Atmosphere or Vacuum: A Comparative Study

During the last decades, the consumption of bamboo sprouts (Phyllostacys edulis) has increased because they are considered a “superfood”. However, this product is characterized by a short shelf life due to the deterioration in quality parameters. The aim of this study was to investigate the application of two modified atmosphere packaging (MAP) systems (MAP1: 2% O2, 5% CO2, 93% N2 and MAP2: 3% O2, 7% CO2, 90% N2) to fresh-shelled ready-to-eat bamboo sprouts and compare these packaging systems with vacuum packaging during storage for 28 days at 4 °C using heat-sealable polyamide and polyethylene (PA/PE) trays. Several chemical-physical parameters (moisture content, water activity, pH, headspace composition, and firmness) were monitored, as well as CIELab colorimetric parameters and microbial growth. The quantification of selected organic acids was performed via UHPLC. Mathematical kinetic models were applied to study the evolution of total phenol (TPC), flavonoid (TFC), and carotenoid content (TCC) during storage. The evolution of antioxidant potential investigated by ABTS, DPPH, and β-carotene bleaching tests was also assessed. Results showed that at the end of the storage period, significant variations in the colorimetric parameters are detectable between the sprouts apical portion and the basal one, regardless of both applied MAPs. A linear reduction in both DPPH and ABTS radical scavenging activity was evidenced during storage, regardless of the type of packaging applied. In DPPH test samples packaged in MAP after 28 days of storage, they retain good antioxidant activity, whereas in vacuum, this activity is reduced by 50% compared to the initial value (IC50 values from 24.77 to 32.74 μg/mL and from 24.77 to 71.12 μg/mL for MAP2 and vacuum, respectively)

Combined pharmacological and psychosocial interventions for alcohol use disorder

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and safety of combined pharmacological and psychosocial interventions for the treatment of alcohol use disorder

Formation of amides: one-pot condensation of carboxylic acids and amines mediated by TiCl4

Abstract A general procedure for the synthesis of amides via the direct condensation of carboxylic acids and amines in the presence of TiCl4 is reported. The amidation reaction was performed in pyridine at 85 °C with a wide range of substrates providing the corresponding amide products in moderate to excellent yields and high purity. The reaction proceeds with low yields when both the carboxylic acid and the amine are sterically hindered. The process takes place with nearly complete preservation of the stereochemical integrity of chiral substrates

N-methylated α-amino acids and peptides: synthesis and biological activity

The simplest and minimal modification of a single amino acid or peptide bonds is represented by N-methylation. This can improve the pharmacokinetic properties of biologically active peptides as well as resulting in analogues that show specific biological activity such as enzyme inhibitors, receptor antagonists and agonists, building blocks in combinatorial chemistry for the screening of new potential drugs. Further, structural and conformational studies performed with N-methylated analogues of natural amino acids and peptides enabled to (i) produce stable foldamers with different topology with respect to the helix of natural and endogenous peptides, (ii) confer to modified peptides high stability against proteases and (iii) enhance lipophilicity and bioavailability for pharmacological purposes. Consequentially, it is crucial to provide optically pure N-methyl-amino acids and N-methylated peptides with a large supply. The present report will focus on the results obtained in the last decade in the field of chemical synthetic methodologies for the N-methylation of amino acids

Pseudotumor cerebri as presenting syndrome of Addisonian crisis

In a patient who developed clinical signs of intracranial hypertension, bilateral papilledema and diplopia, in association with mild hypotension, hyponatremia and hyperkalemia, the hypothesis of Addison's disease was raised and confirmed. Substitutional therapy led to complete recovery. The present paper represents the first report of pseudotumor cerebri as the only clinical sign of an Addisonian crisis

Leptin-Activity Modulators and Their Potential Pharmaceutical Applications

Leptin, a multifunctional hormone primarily, but not exclusively, secreted in adipose tissue, is implicated in a wide range of biological functions that control different processes, such as the regulation of body weight and energy expenditure, reproductive function, immune response, and bone metabolism. In addition, leptin can exert angiogenic and mitogenic actions in peripheral organs. Leptin biological activities are greatly related to its interaction with the leptin receptor. Both leptin excess and leptin deficiency, as well as leptin resistance, are correlated with different human pathologies, such as autoimmune diseases and cancers, making leptin and leptin receptor important drug targets. The development of leptin signaling modulators represents a promising strategy for the treatment of cancers and other leptin-related diseases. In the present manuscript, we provide an update review about leptin-activity modulators, comprising leptin mutants, peptide-based leptin modulators, as well as leptin and leptin receptor specific monoclonal antibodies and nanobodies