On the preparation of carbohydrate-protein conjugates using the traceless Staudinger ligation

[reaction: see text] The nature of a linker used for preparing glycoconjugate vaccines is of utmost importance as it may lead to immunogenic biomolecules. We report the conjugation of carbohydrate haptens to protein carriers leading to potential vaccines using the traceless Staudinger ligation. The ligation relies on the selective transfer of a phosphane substituent to an azide to form a native amide bond in the final product upon release of an oxidized phosphane byproduct. We designed new phosphino-functionalized cross-linkers suitable for protein carrier derivatization. We evaluated their utility in preparing conjugates using both synthetic and purified bacterial carbohydrates. The use of a borane-protected phosphane which is deprotected at the time of the ligation reaction led to the best results observed thus far in terms of stability toward oxidation and reactivity.     

Synthesis,conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp2-iminosugar fragment

The Tn antigen (GalNAc-α-1-O-Thr/Ser) is a well-known tumor-associated carbohydrate determinant. The use of glycopeptides that incorporate this structure has become a significant and promising niche of research owing to their potential use as anticancer vaccines. Herein, the conformational preferences of a glycopeptide with an unnatural Tn antigen, characterized by a threonine decorated with an sp²-iminosugar-type α-GalNAc mimic, have been studied both in solution, by combining NMR spectroscopy and molecular dynamics simulations, and in the solid state bound to an anti-mucin-1 (MUC1) antibody, by X-ray crystallography. The Tn surrogate can mimic the main conformer sampled by the natural antigen in solution and exhibits high affinity towards anti-MUC1 antibodies. Encouraged by these data, a cancer vaccine candidate based on this unnatural glycopeptide and conjugated to the carrier protein Keyhole Limpet Hemocyanin (KLH) has been prepared and tested in mice. Significantly, the experiments in vivo have proved that this vaccine elicits higher levels of specific anti-MUC1 IgG antibodies than the analog that bears the natural Tn antigen and that the elicited antibodies recognize human breast cancer cells with high selectivity. Altogether, we compile evidence to confirm that the presentation of the antigen, both in solution and in the bound state, plays a critical role in the efficacy of the designed cancer vaccines. Moreover, the outcomes derived from this vaccine prove that there is room for exploring further adjustments at the carbohydrate level that could contribute to designing more efficient cancer vaccines.

An anti-cancer vaccine based on an unnatural antigen with an sp²-iminosugar fragment.     

Synthesis and Thermal Study of Magnesium Complexes with 8-hydroxyquinolinate Derivatives

Magnesium ion was reacted with 5,7-dibromo-, 5,7-dichloro-, 7-iodo-and 5-chloro-7-iodo-8-hydroxyquinoline, in acetone/ammonium hydroxide medium under constant stirring to obtain (I) Mg[(C₉H₄ONBr₂)₂]·2H₂O; (II) Mg[(C₉H₄ONCl₂)₂]·3H₂O; (III) Mg[(C₉H₅ONI)₂]·2H₂O and (IV)Mg[(C₉H₄ONICl)₂]·2.5H₂O complexes. The compounds were characterized by elemental analysis, IR spectra, ICP, TG-DTA and DSC. Through thermal decomposition residues were obtained and characterized, by X-ray diffractometry, as a mixture of hexagonal MgBr₂ and cubic MgO to the (I) compound at 850°C; cubic MgO to the (II), (III) and (IV) compounds at750, 800 and 700°C, respectively. This revised version was published online in July 2006 with corrections to the Cover Date.     

Drying Effects on Chemical Composition and Antioxidant Activity of Lippia thymoides Essential Oil,a Natural Source of Thymol

Leaves of Lippia thymoides (Verbenaceae) were dried in an oven at 40, 50 and 60 °C and the kinetic of drying and the influence of the drying process on the chemical composition, yield, and DPPH radical scavenging activity of the obtained essential oils were evaluated. The composition of the essential oils was determined with gas chromatography-mass spectrometry and gas chromatography-flame ionization detection analyses. The influence of drying on the chemical composition of the essential oils of L. thymoides was evaluated by multivariate analysis, and their antioxidant activity was investigated via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The Midilli model was the most appropriate to describe the behavior of drying kinetic data of L. thymoides leaves. Thymol was the major compound for all analyzed conditions; the maximum content was obtained from fresh leaves (62.78 ± 0.63%). The essential oils showed DPPH radical scavenging activity with an average of 73.10 ± 12.08%, and the fresh leaves showed higher inhibition (89.97 ± 0.31%). This is the first study to evaluate the influence of drying on the chemical composition and antioxidant activity of L. thymoides essential oils rich in thymol.     

Asymptotic expansions,L-values and a new quantum modular form

In 2010, Zagier introduced the notion of a quantum modular form. One of his first examples was the “strange” function F(q) of Kontsevich. Here we produce a new example of a quantum modular form by making use of some of Ramanujan’s mock theta functions. Using these functions and their transformation behaviour, we also compute asymptotic expansions similar to expansions of F(q).     

Heuristic analysis of <Emphasis Type="Italic">Eucalyptus globulus</Emphasis> bark depolymerization via acid-liquefaction

A clear, direct and rapid analysis of the preliminary results concerning the acid liquefaction of Eucalyptus globulus’ bark is herein presented. The results led to a methodology for the selective liquefaction of hemicellulose and amorphous cellulose. Liquefaction was conducted at various temperatures, as well as different reaction times. The process results are heuristically explained in view of the experiments of ATR-FTIR, hydroxyl number, and acid value. The procedure method allows reusing the wastes arising from the paper industry. Valuable products and chemical building blocks from lignocellulosic biomass, mostly based on cellulose can be thus accessed.     

Characterization of an electrochemical mercury sensor using alternating current,cyclic, square wave and differential pulse voltammetry

Here we report the characterization of an electrochemical mercury (Hg²⁺) sensor constructed with a methylene blue (MB)-modified and thymine-containing linear DNA probe. Similar to the linear probe electrochemical DNA sensor, the resultant sensor behaved as a “signal-off” sensor in alternating current voltammetry and cyclic voltammetry. However, depending on the applied frequency or pulse width, the sensor can behave as either a “signal-off” or “signal-on” sensor in square wave voltammetry (SWV) and differential pulse voltammetry (DPV). In SWV, the sensor showed “signal-on” behavior at low frequencies and “signal-off” behavior at high frequencies. In DPV, the sensor showed “signal-off” behavior at short pulse widths and “signal-on” behavior at long pulse widths. Independent of the sensor interrogation technique, the limit of detection was found to be 10 nM, with a linear dynamic range between 10 nM and 500 nM. In addition, the sensor responded to Hg²⁺ rather rapidly; majority of the signal change occurred in <20 min. Overall, the sensor retains all the characteristics of this class of sensors; it is reagentless, reusable, sensitive, specific and selective. This study also highlights the feasibility of using a MB-modified probe for real-time sensing of Hg²⁺, which has not been previously reported. More importantly, the observed “switching” behavior in SWV and DPV is potentially generalizable and should be applicable to most sensors in this class of dynamics-based electrochemical biosensors.     

The impact of the natural sciences on archaeology

This article reviews some of the applications of physics to the solution of archaeological problems. The use of magnetic, resistivity and electromagnetic surveying techniques for the location of buried features is described. Various methods of age determination are outlined while the problems associated with radiocarbon dating of organic material and thermoluminescent dating of pottery are discussed in detail. The techniques, including petrological examination, chemical analysis and isotopic analysis, employed in the physical examination of archaeological artefacts are described. Examples of the application of these techniques in establishing the source of the raw materials used in pottery, metal and stone implements and in elucidating the techniques of manufacture of pottery and metal objects are also given.