Unlocking nature's antioxidants: a novel method for synthesising plasmalogens.

Plasmalogens are glycerophospholipids distinguished by their -()-vinyl ether at the -1 position. These lipids are implicated in several disease states requiring analytical, diagnostic and therapeutic interventions, which demand synthetic availability for a variety of structural types. By deploying the new -protecting group 1,4-dimethoxynaphthyl-2-methyl ('DIMON') and a new stereospecific method for accessing -vinyl ethers, a reproducible, versatile synthetic route to plasmalogens [plasmenyl phosphocholines] has been developed.

1,4-Dimethoxynaphthalene-2-methyl ('DIMON'), an oxidatively labile protecting group for synthesis of polyunsaturated lipids.

A new benzyl-type protecting group (1,4-dimethoxynaphthalene-2-methyl, 'DIMON') for hydroxyl functions can be selectively removed under oxidative conditions without damaging polyunsaturated fatty acyl groups. Its application is shown by the first synthesis of an ether (plasmanyl) phospholipid containing the docosa-(4,7,10,13,16,19)-hexaenoyl group.

Harnessing the Peterson Reaction for the Stereospecific Synthesis of Z-Vinyl Ethers.

Vinyl ethers are valuable synthetic intermediates which are also found as natural products, including aflatoxins, rifamycins and plasmalogens. The latter are ubiquitous phospholipids in human cells and contain a vinyl ether moiety with specifically Z configuration. Although numerous methods are available for synthesis of vinyl ethers, there is a lack of methods for obtaining Z isomers of molecules of the type RCH=CHOR' that are applicable to plasmalogens.

Two Key Amino Acids Variant of α-l-arabinofuranosidase from Str. 168 with Altered Activity for Selective Conversion Ginsenoside Rc to Rd.

α-l-arabinofuranosidase is a subfamily of glycosidases involved in the hydrolysis of l-arabinofuranosidic bonds, especially in those of the terminal non-reducing arabinofuranosyl residues of glycosides, from which efficient glycoside hydrolases can be screened for the transformation of ginsenosides. In this study, the ginsenoside Rc-hydrolyzing α-l-arabinofuranosidase gene, was cloned from and its codons were optimized for efficient expression in BL21 (DE3). The recombinant protein BsAbfA fused with an N-terminal His-tag was overexpressed and purified, and then subjected to enzymatic characterization.

Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein-Protein Interaction.

Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design of novel isoindolinone-based MDM2 inhibitors. MDM2 X-ray crystallography, quantum mechanics ligand-based design, and metabolite identification all contributed toward the discovery of potent and inhibitors of the MDM2-p53 interaction with representative compounds inducing cytostasis in an SJSA-1 osteosarcoma xenograft model following once-daily oral administration.

Molecular Diversity via Tetrasubstituted Alkenes Containing a Barbiturate Motif: Synthesis and Biological Activity.

The synthesis of a molecularly diverse library of tetrasubstituted alkenes containing a barbiturate motif is described. Base-induced condensation of -substituted pyrimidine-2,4,6(1,3,5)-triones with 5-(bis(methylthio)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-substituted 5-(methylthio)-2-pyrano[2,3-]pyrimidine-2,4,7(1,3)-triones ('pyranopyrimidinones'), regioselectively. A sequence of reactions involving ring-opening of the pyran moiety, displacement of the methylthio group with an amine, re-formation of the pyran ring, and after its final cleavage with an amine, gave tetrasubstituted alkenes (3-amino-3-(2,4,6-trioxotetrahydropyrimidin-5(2)-ylidene)propanamides) with a diversity of substituents.

Co-delivery of gambogenic acid and VEGF-siRNA with anionic liposome and polyethylenimine complexes to HepG2 cells.

The combination of two or more different mechanisms of drugs in the treatment of cancer has become one of the effective methods. The purpose of this study was to successfully prepare a non-viral delivery system that could efficiently co-delivery siRNA and gambogenic acid (GNA) to improve the anti-cancer efficiency in HepG2 cells. The delivery system was prepared by a two-step method.

[Relationship between fishing grounds temporal-spatial distribution of Thunnus obesus and thermocline characteristics in the Western and Central Pacific Ocean].

A thermocline characteristics contour on a spatial overlay map was plotted using data collected on a monthly basis from Argo buoys and data of monthly CPUE (catch per unit effort) bigeye tuna (Thunnus obesus) long-lines fishery from the Western and Central Pacific Fisheries Commission (WCPFC) to evaluate the relationship between fishing grounds temporal-spatial distribution of bigeye tuna and thermocline characteristics in the Western and Central Pacific Ocean (WCPO). In addition, Numerical methods were used to calculate the optimum ranges of thermocline characteristics of the central fishing grounds. The results showed that the central fishing grounds were mainly distributed between 10° N and 10° S.

Synthesis, characterization, thermal properties and antiproliferative potential of copper(II) 4'-phenyl-terpyridine compounds.

Reactions between 4'-phenyl-terpyridine (L) and several Cu(II) salts (p-toluenesulfonate, benzoate and o-, m- or p-hydroxybenzoate) led to the formation of [Cu(p-SO3C6H4CH3)L(H2O)2](p-SO3C6H4CH3) (1), [Cu(OCOPh)2L] (2), [Cu(o-OCOC6H4OH)2L] (3), [Cu(m-OCOC6H4OH)2L]4·MeOH (·MeOH) and [Cu(p-OCOC6H4OH)2L]5·2H2O (·2H2O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N3O3 octahedral coordination geometries, which, in 2-5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular π···π stacking interactions could also be found in 2-5 (in the 3.

Small-molecule MDM2-p53 inhibitors: recent advances.

Potent and selective small-molecule inhibitors of the p53-MDM2 interaction intended for the treatment of p53 wild-type tumors have been designed and optimized in a number of chemical series. This review details recent disclosures of compounds in advanced optimization and features key series that have given rise to clinical trial candidates. The structure-activity relationships for inhibitor classes are discussed with reference to x-ray structures, and common structural features are identified.

Detection of 3D curved trajectories: the role of binocular disparity.

We examined the ability of observers to detect the 3D curvature of motion paths when binocular disparity and motion information were present. On each trial, two displays were observed through shutter-glasses. In one display, a sphere moved along a linear path in the horizontal and depth dimensions.

Coatings of one monomer molecularly imprinted polymers for open tubular capillary electrochromatography.

One monomer molecularly imprinted polymer coatings were first synthesized in fused silica capillary columns with 2-methacrylamidopropyl methacrylate (MAM) as single functional monomer in addition to a cross-linking monomer. Since MAM may generate no or little EOF, a strategy of precursor of polymerization, which does not interfere with the formation of defined imprints, was used to introduce an ionizable functional monomer to generate a stable electroosmotic flow for electrochromatography (CEC) by post-polymerization hydrolization. The resulting MAM-based open-tubular imprinted capillary was able to separate enantiomers by means of CEC.

Fractal feature extraction of marrow cell images.

An algorithm based on the cell image center of gravity and its scaleless range (as scale-invariant) is proposed to estimate the fractal dimension of the marrow cell images. Since the texture of a color image contains not only certain statistical similarity on the structure but also the color distributions, two color parameters are extracted from the color images of marrow cells for the fractal dimension calculation. An efficient approach is described for the discrimination between different marrow cells with the combination of the fractal dimension.