Synthesis and structure revision of tyroscherin, a growth inhibitor of IGF-1-dependent tumor cells

Synthesis of the proposed structure of tyroscherin, a growth inhibitor of IGF-1-dependent cancer cells, was succeeded by one-pot Julia coupling. However, spectral data of the synthetic compound were not identical with those of natural tyroscherin. The stereochemistry of tyroscherin was revised to be 2S,3R,8R,10R by syntheses of stereoisomers.     

Towards the biotechnological isomerization of branched sugars: d-tagatose-3-epimerase equilibrates both enantiomers of 4-C-methyl-ribulose with both enantiomers of 4-C-methyl-xylulose

Microbial oxidation of 2-C-methyl-d-ribitol and 2-C-methyl-d-arabinitol by Gluconobacter thailandicus NBRC 3254 produces 4-C-methyl-l-ribulose and 4-C-methyl-d-ribulose, respectively. Further, 4-C-methyl-l-ribulose and 4-C-methyl-d-ribulose were equilibrated by d-tagatose-3-epimerase (DTE) with 4-C-methyl-l-xylulose and 4-C-methyl-d-xylulose, respectively. These transformations demonstrate that polyol dehydrogenase and DTE act on branched synthetic sugars. The green preparation of all of the stereoisomers of 4-C-methyl pentuloses illustrates the ability of biotechnology to generate novel branched monosaccharides.     

Acid-base bifunctional catalysis of silica-alumina-supported organic amines for carbon-carbon bond-forming reactions

Acid-base bifunctional heterogeneous catalysts were prepared by the reaction of an acidic silica-alumina (SA) surface with silane-coupling reagents possessing amino functional groups. The obtained SA-supported amines (SA-NR2) were characterized by solid-state 13C and 29Si NMR spectroscopy, FT-IR spectroscopy, and elemental analysis. The solid-state NMR spectra revealed that the amines were immobilized by acid-base interactions at the SA surface. The interactions between the surface acidic sites and the immobilized basic amines were weaker than the interactions between the SA and free amines. The catalytic performances of the SA-NR2 catalysts for various carbon-carbon bond-forming reactions, such as cyano-ethoxycarbonylation, the Michael reaction, and the nitro-aldol reaction, were investigated and compared with those of homogeneous and other heterogeneous catalysts. The SA-NR2 catalysts showed much higher catalytic activities for the carbon-carbon bond-forming reactions than heterogeneous amine catalysts using other supports, such as SiO2 and Al2O3. On the other hand, homogeneous amines hardly promoted these reactions under similar reaction conditions, and the catalytic behavior of SA-NR2 was also different from that of MgO, which was employed as a typical heterogeneous base. An acid-base dual-activation mechanism for the carbon-carbon bond-forming reactions is proposed.     

Recent applications of capillary electrophoresis-mass spectrometry (CE-MS): CE performing functions beyond separation

Capillary electrophoresis is one of the separation tools commonly used in conjugation with mass spectrometry. Its primary purpose is to resolve the components in a sample mixture prior to mass spectral identification. Moreover, an increasing number of applications reported in the literature involve the use of CE for additional purposes, such as sample preparation and derivatization, and the study of biochemical properties. This review provides an overview on the various roles of CE beyond that of a simple separation tool. While the scope focuses on the area of interest rather than a predefined time period, the majority of the references highlighted were initially published within the past five years.     

Prediction of cyclooxygenase inhibitory activity of curcuma rhizome from chromatograms by multivariate analysis

The potential use of partial least square regression (PLS-R) models for the prediction of biological activities of a herbal drug based on its liquid chromatography (LC) profile was verified using various extracts of Curcuma phaeocaulis and their cyclooxygenase-2 (COX-2) inhibitory activities as the model experiment. The correlation of practically measured inhibitory activities and predicted values by PLS-R analysis was quite good (correlation coefficient=0.9935) and the possibility of transforming chromatographic information into a measure of biological activity was confirmed. In addition, furanodienone and curcumenol were identified as the major active anti-inflammatory constituents of C. phaeocaulis, through detailed analysis of the regression vector, followed by isolation of these compounds and their COX-2 inhibitory assays. The selectivity indices (SI), IC(50) of COX-1/IC(50) of COX-2, of both compounds were higher than that of indomethacin and it is considered that furanodienone and curcumenol are the most promising compounds as lead anti-inflammatory agents.     

Conducting dimerized cobalt complexes with tetrathiafulvalene dithiolate ligands

To obtain novel single-component molecular metals, we attempted to synthesize several cobalt complexes coordinated by TTF (tetrathiafulvalene)-type dithiolate ligands. We succeeded in the syntheses and structure determinations of ((n)Bu(4)N)(2)[Co(chdt)(2)](2) (1), ((n)Bu(4)N)(2)[Co(dmdt)(2)](2) (2), [Co(dmdt)(2)](2) (3), and [Co(dt)(2)](2) (4) (chdt = cyclohexeno-TTF-dithiolate, dmdt = dimethyl-TTF-dithiolate, and dt = TTF-dithiolate). Structure analyses of complexes 1-4 revealed that two monomeric [Co(ligand)2]- or [Co(ligand)(2)](0) units are connected by two Co-S bonds resulting in dimeric [Co(ligand)(2)](2)(2-) or [Co(ligand)(2)](2) molecules. Complex 1 has a cation-anion-intermingled structure and exhibited Curie-Weiss magnetic behavior with a large Curie constant (C = 2.02 K x emu x mol(-1)) and weak antiferromagnetic interactions (theta = -8.3 K). Complex 2 also has a cation-anion-intermingled structure. However, the dimeric molecules are completely isolated by cations. Complexes 3 and 4 are single-component molecular crystals. The molecules of complex 3 form two-dimensional molecular stacking layers and exhibit a room-temperature conductivity of sigmart = 1.2 x 10(-2) S.cm(-1) and an activation energy of E(a) = 85 meV. The magnetic behavior is almost consistent with Curie-Weiss law, where the Curie constant and Weiss temperature are 8.7 x 10(-2) K x emu x mol(-1) and -0.85 K, respectively. Complex 4 has a rare chair form of the dimeric structure. The electrical conductivity was fairly large (sigmart = 19 S.cm(-1)), and its temperature dependence was very small (sigma(0.55K)/sigma(rt) = ca. 1:10), although the measurements were performed on the compressed pellet sample. Complex 4 showed an almost constant paramagnetic susceptibility (chi(300) (K) = 3.5 x 10(-4) emu x mol(-1)) from 300 to 50 K. The band structure calculation of complex 4 suggested the metallic nature of the system. Complex 4 is a novel single-component molecular conductor with a dimeric molecular structure and essentially metallic properties down to very low temperatures.     

PAP inhibitor with in vivo efficacy identified by Candida albicans genetic profiling of natural products

Natural products provide an unparalleled source of chemical scaffolds with diverse biological activities and have profoundly impacted antimicrobial drug discovery. To further explore the full potential of their chemical diversity, we survey natural products for antifungal, target-specific inhibitors by using a chemical-genetic approach adapted to the human fungal pathogen Candida albicans and demonstrate that natural-product fermentation extracts can be mechanistically annotated according to heterozygote strain responses. Applying this approach, we report the discovery and characterization of a natural product, parnafungin, which we demonstrate, by both biochemical and genetic means, to inhibit poly(A) polymerase. Parnafungin displays potent and broad spectrum activity against diverse, clinically relevant fungal pathogens and reduces fungal burden in a murine model of disseminated candidiasis. Thus, mechanism-of-action determination of crude fermentation extracts by chemical-genetic profiling brings a powerful strategy to natural-product-based drug discovery.     

Nanorheology measurement on single circularly permuted green fluorescent protein molecule

The force measurement mode of an atomic force microscope (AFM) has enabled us to measure the mechanical properties of biological materials at the single molecular level. In a conventional quasi-static force measurement on a single circularly permuted green fluorescent protein (cpGFP), we could unfold it by unraveling several sub-domains in a distinct sawtooth pattern at a slow stretching speed. In order to elucidate more detailed conformational changes at each extension length, we further measured dynamic relax-stress response of cpGFP molecules. In this measurement, several cycles of sinusoidal movement were applied to the sample during the stretching process. We found the protein molecule showed in-phase response to the sinusoidal input in most case of measurements.     

Chromium(III) complexes as intermolecular probes

Metal ion complexes provide flexible paramagnetic centers that may be used to define intermolecular contacts in a variety of solution phase environments because both the charge and electronic relaxation properties of the complex may be varied. For most complex ions, there are several proton equilibria that may change the effective charge on the complex as a function of pH which in turn affects the efficacy of application for defining the electrostatic surfaces of co-solute molecules. We report here spectrophotometric and nuclear spin relaxation studies on aqueous solutions of chromium(III) complexes of EDTA, DTPA, and bis-amides of both. The effective charges available from these paramagnetic centers range from -3 to +1 and we report the pH ranges over which the effective charge is defined with confidence for application in magnetic relaxation experiments.