Copper Reactivity Can Be Tuned to Catalyze the Stereoselective Synthesis of 2-Deoxyglycosides from Glycals.

We demonstrate that tuning the reactivity of Cu by the choice of oxidation state and counterion leads to the activation of both "armed" and "disarmed" type glycals toward direct glycosylation leading to the α-stereoselective synthesis of deoxyglycosides in good to excellent yields. Mechanistic studies show that CuI is essential for effective catalysis and stereocontrol and that the reaction proceeds through dual activation of both the enol ether as well as the OH nucleophile.

Protozoan Parasites Glycosylphosphatidylinositol Anchors: Structures, Functions and Trends for Drug Discovery.

BACKGROUND: Glycosylphosphatidylinositol (GPI) anchors are molecules located on cell membranes of all eukaryotic organisms. Proteins, enzymes, and other macromolecules which are anchored by GPIs are essential elements for interaction between cells, and are widely used by protozoan parasites when compared to higher eukaryotes. METHODS: More than one hundred references were collected to obtain broad information about mammalian and protozoan parasites' GPI structures, biosynthetic pathways, functions and attempts to use these molecules as drug targets against parasitic diseases. Differences between GPI among species were compared and highlighted. Strategies for drug discovery and development against protozoan GPI anchors were discussed based on what has been reported on literature. RESULTS: There are many evidences that GPI anchors are crucial for parasite's survival and interaction with hosts' cells. Despite all GPI anchors contain a conserved glycan core, they present variations regarding structural features and biosynthetic pathways between organisms, which could offer adequate selectivity to validate GPI anchors as drug targets. Discussion was developed with focus on the following parasites: Trypanosoma brucei, Trypanosoma cruzi, Leishmania, Plasmodium falciparum and Toxoplasma gondii, causative agents of tropical neglected diseases. CONCLUSION: This review debates the main variances between parasitic and mammalian GPI anchor biosynthesis and structures, as well as clues for strategic development for new anti-parasitic therapies based on GPI anchors.

Trypanosoma cruzi Invasion into Host Cells: A Complex Molecular Targets Interplay.

Chagas' disease is still a worldwide threat, with estimated from 6 to 7 million infected people, mainly in Latin America. Despite all efforts, especially from international consortia (DNDi, NMTrypI), to develop an innovative therapeutic strategy against this disease, no candidate has achieved full requirements for clinical use yet. In this review, we point out the general molecular and cellular mechanisms involved in T. cruzi cell invasion and elucidate the roles of specific parasite and host targets in the progress of Chagas' disease. Among these molecular targets are Gp85/transsialidase, mucins, cruzipain and oligopeptidase B, found in parasite cell surface, and Galectin-3 and Toll-like receptors present in host cells. Thus, the deep understanding of their interplay and involvement on T. cruzi host cell adhesion, invasion and evasion from host immune may expand the chances for discovering new therapeutic agents against this neglected disease. Additionally, these targets may represent a remarkable strategy to block parasite invasion in the early stages of infection.

Method validation for control determination of mercury in fresh fish and shrimp samples by solid sampling thermal decomposition/amalgamation atomic absorption spectrometry.

A method for the determination of total mercury in fresh fish and shrimp samples by solid sampling thermal decomposition/amalgamation atomic absorption spectrometry (TDA AAS) has been validated following international foodstuff protocols in order to fulfill the Brazilian National Residue Control Plan. The experimental parameters have been previously studied and optimized according to specific legislation on validation and inorganic contaminants in foodstuff. Linearity, sensitivity, specificity, detection and quantification limits, precision (repeatability and within-laboratory reproducibility), robustness as well as accuracy of the method have been evaluated. Linearity of response was satisfactory for the two range concentrations available on the TDA AAS equipment, between approximately 25.0 and 200.0 µg kg(-1) (square regression) and 250.0 and 2000.0 µg kg(-1) (linear regression) of mercury. The residues for both ranges were homoscedastic and independent, with normal distribution. Correlation coefficients obtained for these ranges were higher than 0.995. Limits of quantification (LOQ) and of detection of the method (LDM), based on signal standard deviation (SD) for a low-in-mercury sample, were 3.0 and 1.0 µg kg(-1), respectively. Repeatability of the method was better than 4%. Within-laboratory reproducibility achieved a relative SD better than 6%. Robustness of the current method was evaluated and pointed sample mass as a significant factor. Accuracy (assessed as the analyte recovery) was calculated on basis of the repeatability, and ranged from 89% to 99%. The obtained results showed the suitability of the present method for direct mercury measurement in fresh fish and shrimp samples and the importance of monitoring the analysis conditions for food control purposes. Additionally, the competence of this method was recognized by accreditation under the standard ISO/IEC 17025.