Stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine [Jaspine B]

A practical stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B) was achieved in 48% overall yield from D-(-)-tartaric acid. Key features of the sequence include the diastereoselective formation of a tetrol with three contiguous chiral centers, which was further elaborated to pachastrissamine. The synthetic route is operationally simple, diastereoselective and is amenable for the synthesis of a number of analogues of pachastrissamine.

Characteristics of field-effect transistors based on undoped and B-and N-doped few-layer graphenes

Field-effect transistor characteristics of few-layer graphenes prepared by several methods have been investigated in comparison with those of single-layer graphene prepared by the in situ reduction of single-layer graphene oxide. Ambipolar features have been observed with single-layer graphene and n-type behaviour with all the few-layer graphenes, the best characteristics being found with the graphene possessing 2-3 layers prepared by arc-discharge of graphite in hydrogen. FETs based on boron and nitrogen doped graphene show n-type and p-type behaviour respectively. (C) 2010 Elsevier Ltd. All rights reserved.

Specificity for the Exchange of Phospholipids Through Polymyxin B Mediated Intermembrane Molecular Contacts

Structural specificity for the direct vesicle−vesicle exchange of phospholipids through stable molecular contacts formed by the antibiotic polymyxin B (PxB) is characterized by kinetic and spectroscopic methods. As shown elsewhere [Cajal, Y., Rogers, J., Berg, O. G., & Jain, M. K. (1996) Biochemistry 35, 299−308], intermembrane molecular contacts between anionic vesicles are formed by a small number of PxB molecules, which suggests that a stoichiometric complex may be responsible for the exchange of phospholipids. Larger clusters containing several vesicles are formed where each vesicle can make multiple contacts if sterically allowed. In this paper we show that the overall process can be dissected into three functional steps: binding of PxB to vesicles, formation of stable vesicle−vesicle contacts, and exchange of phospholipids. Polycationic PxB binds to anionic vesicles. Formation of molecular contacts and exchange of monoanionic phospholipids through PxB contacts does not depend on the chain length of the phospholipid. Only monoanionic phospholipids (with methanol, serine, glycol, butanol, or phosphatidylglycerol as the second phosphodiester substituent in the head group) exchange through these contacts, whereas dianionic phosphatidic acid does not. Selectivity for the exchange was also determined with covesicles of phosphatidylmethanol and other phospholipids. PxB does not bind to vesicles of zwitterionic phosphatidylcholine, and its exchange in covesicles is not mediated by PxB. Vesicles of dianionic phospholipids, like phosphatidic acid, bind PxB; however, this phospholipid does not exchange. The structural features of the contacts are characterized by the spectroscopic and chemical properties of PxB at the interface. PxB in intermembrane contacts is readily accessible from the aqueous phase to quenchers and reagents that modify amino groups. Results show that PxB at the interface can exist in two forms depending on the lipid/PxB ratio. Additional studies show that stable PxB-mediated vesicle−vesicle contacts may be structurally and functionally distinct from “stalks”, the putative transient intermediate for membrane fusion. The phenomenon of selective exchange of phospholipids through peptide-mediated contacts could serve as a prototype for intermembrane targeting and sorting of phospholipids during their biosynthesis and trafficking in different compartments of a cell. The protocols and results described here also extend the syllogistic foundations of interfacial equilibria and catalysis.

Carbohydrate binding specificity of the B-cell maturation mitogen from Artocarpus integrifolia seeds

Artocarpin, a mannose-specific lectin, is a homotetrameric protein (M(r) 65,000) devoid of covalently attached carbohydrates and consists of four isolectins with pI in the range 5-6.5. Investigations of its carbohydrate binding specificity reveal that among monosaccharides, mannose is preferred over glucose. Among mannooligosaccharides, mannotriose (Man alpha 1-3[Man alpha 1-6]Man) and mannopentaose are the strongest ligands followed by Man alpha 1-3Man. Extension of these ligands by GlcNAc at the reducing ends of mannooligosaccharides tested remarkably improves their inhibitory potencies, while substitution of both the alpha 1-3 and alpha 1-6 mannosyl residues of mannotriose and the core pentasaccharide of N-linked glycans (Man alpha 1-3[Man alpha 1-6]Man beta 1-4GlcNAc beta 1-4GlcNAc) by GlcNAc or N-acetyllactosamine in beta 1-2 linkage diminishes their inhibitory potencies. Sialylated oligosaccharides are non-inhibitory. Moreover, the substitution of either alpha 1-3 or alpha 1-6 linked mannosyl residues of M5Gn or both by mannose in alpha 1-2 linkage leads to a considerable reduction of their inhibitory power. Addition of a xylose residue in beta 1-2 linkage to the core pentasaccharide improves the inhibitory activity. Considering the fact that artocarpin has the strongest affinity for the xylose containing hepasaccharide from horseradish peroxidase, which differs significantly from all the mannose/glucose-specific lectins, it should prove a useful tool for the isolation and characterization of glycoproteins displaying such structure.

Unusual dielectric response in B-site size-disordered hexagonal transition metal oxides

We discover that hexagonal holmium copper titanate (Ho2CuTiO6), has a unique and highly desirable combination of high dielectric constant, low losses, very small temperature coefficient, and low frequency dependence. Our first-principles calculations indicate that these exceptional properties result from a size-difference at the Cu/Ti B-site that suppresses the expected ferroelectric transition, combined with the dominance of intermediate-frequency polar vibrational modes in the dielectric response. Our results suggest that the use of such B-site disorder in alloys of hexagonal transition-metal oxides should generally result in similar robust dielectrics.

Characterization of two M17 family members in Escherichia coli, Peptidase A and Peptidase B

Escherichia coil encodes two aminopeptidases belonging to the M17 family: Peptidase A (PepA) and Peptidase B (PepB). To gain insights into their substrate specificities, PepA or PepB were overexpressed in Delta pepN, which shows greatly reduced activity against the majority of amino acid substrates. Overexpression of PepA or PepB increases catalytic activity of several aminopeptidase substrates and partially rescues growth of Delta pepN during nutritional downshift and hightemperature stress. Purified PepA and PepB display broad substratespecificity and Leu, Lys, Met and Gly are preferred substrates. However, distinct differences are observed between these two paralogs: PepA is more stable at high temperature whereas PepB displays broader substrate specificity as it cleaves Asp and insulin B chain peptide. Importantly, this strategy, i.e. overexpression of peptidases in Delta pepN and screening a panel of substrates for cleavage, can be used to rapidly identify peptidases with novel substrate specificities encoded in genomes of different organisms. (C) 2010 Elsevier Inc. All rights reserved.

Non-linear couette flow with heat transfer using the B-G-K model

In recent years a large number of investigators have devoted their efforts to the study of flow and heat transfer in rarefied gases, using the BGK [1] model or the Boltzmann kinetic equation. The velocity moment method which is based on an expansion of the distribution function as a series of orthogonal polynomials in velocity space, has been applied to the linearized problem of shear flow and heat transfer by Mott-Smith [2] and Wang Chang and Uhlenbeck [3]. Gross, Jackson and Ziering [4] have improved greatly upon this technique by expressing the distribution function in terms of half-range functions and it is this feature which leads to the rapid convergence of the method. The full-range moments method [4] has been modified by Bhatnagar [5] and then applied to plane Couette flow using the B-G-K model. Bhatnagar and Srivastava [6] have also studied the heat transfer in plane Couette flow using the linearized B-G-K equation. On the other hand, the half-range moments method has been applied by Gross and Ziering [7] to heat transfer between parallel plates using Boltzmann equation for hard sphere molecules and by Ziering [83 to shear and heat flow using Maxwell molecular model. Along different lines, a moment method has been applied by Lees and Liu [9] to heat transfer in Couette flow using Maxwell's transfer equation rather than the Boltzmann equation for distribution function. An iteration method has been developed by Willis [10] to apply it to non-linear heat transfer problems using the B-G-K model, with the zeroth iteration being taken as the solution of the collisionless kinetic equation. Krook [11] has also used the moment method to formulate the equivalent continuum equations and has pointed out that if the effects of molecular collisions are described by the B-G-K model, exact numerical solutions of many rarefied gas-dynamic problems can be obtained. Recently, these numerical solutions have been obtained by Anderson [12] for the non-linear heat transfer in Couette flow,

1,3,6-Trimethylpyrano[4,3-b]pyrrol-4(1H)-one

All the non-H atoms of the title compound, C10H11NO2, are almost coplanar [maximum deviation = 0.040 (3) angstrom]. The crystal structure is stabilized by C-H center dot center dot center dot O hydrogen bonds.

Constraining scalar leptoquarks from the K and B sectors

Upper bounds at the weak scale are obtained for all lambda(ij)lambda(im) type product couplings of the scalar leptoquark model which may affect K-0 - (K) over bar (0), B-d - (B) over bar (d), and B-s - (B) over bar (s) mixing, as well as leptonic and semileptonic K and B decays. Constraints are obtained for both real and imaginary parts of the couplings. We also discuss the role of leptoquarks in explaining the anomalously large CP-violating phase in B-s - (B) over bar (s) mixing.

Japanese Encephalitis Virus Utilizes the Canonical Pathway To Activate NF-kappa B but It Utilizes the Type I Interferon Pathway To Induce Major Histocompatibility Complex Class I Expression in Mouse Embryonic Fibroblasts

Flaviviruses have been shown to induce cell surface expression of major histocompatibility complex class I (MHC-I) through the activation of NF-kappa B. Using IKK1(-/-), IKK2(-/-), NEMO-/-, and IKK1-/- IKK2-/- double mutant as well as p50(-/-) RelA(-/-) cRel(-/-) triple mutant mouse embryonic fibroblasts infected with Japanese encephalitis virus (JEV), we show that this flavivirus utilizes the canonical pathway to activate NF-kappa B in an IKK2- and NEMO-, but not IKK1-, dependent manner. NF-kappa B DNA binding activity induced upon virus infection was shown to be composed of RelA: p50 dimers in these fibroblasts. Type I interferon (IFN) production was significantly decreased but not completely abolished upon virus infection in cells defective in NF-kappa B activation. In contrast, induction of classical MHC-I (class 1a) genes and their cell surface expression remained unaffected in these NF-kappa B-defective cells. However, MHC-I induction was impaired in IFNAR(-/-) cells that lack the alpha/beta IFN receptor, indicating a dominant role of type I IFNs but not NF-kappa B for the induction of MHC-I molecules by Japanese encephalitis virus. Our further analysis revealed that the residual type I IFN signaling in NF-kappa B-deficient cells is sufficient to drive MHC-I gene expression upon virus infection in mouse embryonic fibroblasts. However, NF-kappa B could indirectly regulate MHC-I expression, since JEV-induced type I IFN expression was found to be critically dependent on it.

Synthesis, X-ray structure and catalytic properties of a copper(II) Schiff base complex modeling the activity of the Cu-B site of dopamine beta-hydroxylase

The copper(II) complex [Cu(salgly) (bpy)] . 4H(2)O (1), where salgly is a tridentate glycinatosalicylaldimine Schiffbase Ligand, is prepared and structurally characterized. The complex is found to be catalytically active in the oxidation of ascorbic acid by dioxygen and the process is also effective in the presence of benzylamine giving benzaldehyde as a product, thus modeling the activity of the Cu-B site of dopamine beta-hydroxylase. (C) 2000 Elsevier Science S.A. All rights reserved.

High-Resolution Magic Angle Spinning Nmr-Studies Of P-31 And B-11 In Fast Ion Conducting Agi-Ag2o-P2o5 And Agi-Ag2o-B2o3 Glasses

Silver iodide-based fast ion conducting glasses containing silver phosphate and silver borate have been studied. An attempt is made to identify the interaction between anions by studying the chemical shifts of31P and11B atoms in high resolution (HR) magic angle spinning (MAS) NMR spectra. Variation in the chemical shifts of31P or11B has been observed which is attributed to the change in the partial charge on the31P or11B. This is indicative of the change in the electronegativity of the anion matrix as a whole. This in turn is interpreted as due to significant interaction among anions. The significance of such interaction to the concept of structural unpinning of silver ions in fast ion conducting glasses is discussed.

Structural alteration from non-B to B-form could reflect DNase I hypersensitivity

Preferential cleavage of active genes by DNase I has been correlated with a structurally altered conformation of DNA at the hypersensitive site in chromatin. To have a better understanding of the structural requirements for gene activation as probed by DNase I action, digestability by DNase I of synthetic polynucleotides having the ability to adopt B and non-B conformation (like Z-form) was studied which indicated a marked higher digestability of the B-form of DNA. Left handed Z form present within a natural sequence in supercoiled plasmid also showed marked resistance towards DNase I digestion. We show that alternating purine-pyrimidine sequences adopting Z-conformation exhibit DNAse I foot printing even in a protein free system. The logical deductions from the results indicate that 1) altered structure like Z-DNA is not a favourable substrate for DNase I, 2) both the ends of the alternating purine-pyrimidine insert showed hypersensitivity, 3) B-form with a minor groove of 12-13 A is a more favourable substrate for DNase I than an altered structure, 4) any structure of DNA deviating largely from B form with a capacity to flip over to the B-form are potential targets for the DNase I enzymic probes in naked DNA.

Diffusion Studies in A(3)B Compounds with A15 Structure

There is a constant effort to understand the defect structure and diffusion behavior in intermetallic compounds with the A15 structure. Diffusion of elements in intermetallic compounds depends mainly on antisites and vacancies on different sublattices. In this article, we shall discuss the diffusion of elements in A(3)B compounds with the A15 structure.