Optimization of tether length in nonglycosidically linked bivalent ligands that target sites 2 and 1 of a Shiga-like toxin

A series of bivalent ligands for a Shiga-like toxin have been synthesized, their experimentally determined inhibitory activities were compared with a simplified thermodynamic model, and computer simulations were used to predict the optimal tether length in bivalent ligands. The design of the inhibitors exploits the proximity of the C-2' hydroxyl groups of two P(k)-trisaccharides when bound to two different, neighboring carbohydrate recognizing binding sites located on the surface of Shiga-like toxin. NMR studies of the complex between the toxin and bivalent ligands show that site 2 and site 1 of a single B subunit are simultaneously occupied by a tethered P(k)-trisaccharide dimer. A simplified thermodynamic treatment provides the intrinsic affinities and binding energies for the intermolecular and intramolecular association events and permits the deconvolution of the contributions to the relative binding energies for the set of bivalent ligands. Conformational analysis based on MD simulations for bivalent galabioside dimers containing different tethers demonstrated that the calculated local concentrations of the pendant ligand at the second binding site correlate with the experimentally determined relative affinity values of the respective bivalent ligands, thereby providing a predictive method to optimize tether length.     

Bismuth triflate-chiral bipyridine complexes as water-compatible chiral Lewis acids

[reaction: see text] Catalytic asymmetric hydroxymethylation of silicon enolates with an aqueous formaldehyde solution has been developed using a chiral bismuth complex. This is the first example of highly enantioselective reactions using a chiral bismuth catalyst in aqueous media. In this paper, we have added Bi(OTf)(3)-1 complex as a "water-compatible Lewis acid". Bi(OTf)3 is unstable in the presence of water but is stabilized by the basic ligand.     

Chromatography of inorganic ions o sulfoethyl cellulose layer in hydrochloric acid and in hydrochloric acid-ammonium thiocyanate media

Summary Chromatographic behavior of 51 inorganic ions has been systematically studied on layers of sulfoethyl (SE) cellulose, a strongly acidic exchanger, in hydrochloric acid and in acid-ammonium thiocyanate media. The sorption of most of the ions on he SE-cellulose decreases with increasing concentration of the acid and the thiocyanate. The characteristic retention of some metal ions of SE-cellulose layer can be recognized over a low concentration of the acid or the salt. Feasibilities for separations of analytical interest are also presented in both systems.     

Thin-layer chromatography of inorganic lons phosphate on cellulose in acetic acid and in acetic acid-ammonium acetate media

Summary Systematic study for the chromatographic behaviour of 49 inorganic ions has been carried out on cellulose phosphate layer in acetic acid and acetic acid — ammonium acetate media. Feasibilities for the effective separations of analytical interest are demonstrated on the 0.25 mm layer in both media.     

Surface control of activated carbon fiber by growth of carbon nanofiber

Carbon nanofiber/activated carbon fiber (CNF/ACF) composites with multifunctional surfaces were prepared through catalytic growth of CNFs on an ACF. Because of selective deposition of catalyst particles in ACF micropores, partial oxidation of ACF after catalyst impregnation was a critical step to control the surface area of the CNF/ACF composites, of which the surface functions can be synergistically performed by both the microporous surface of ACF and free edges of CNFs. CNF/ACF composites of this study are expected to provide an improved performance in SOx or NOx removal.     

Synthesis and Thermal Reaction of 1,3-Bis(alkylseleno)allenes

Reactions of Ph(2)C(3) dianion, prepared from 1,3-diphenylpropyne and n-butyllithium, with dimethyl diselenide and benzylselenocyanate yielded 1,3-bis(methylseleno)-1,3-diphenylpropadiene and 1,3-bis(benzylseleno)-1,3-diphenylpropadiene, respectively, and the reaction with a mixture of dimethyl diselenide and benzylselenocyanate gave 1-benzylseleno-3-methylseleno-1,3-diphenylpropadiene together with the symmetric products. Thermal reactions of the 1,3-bis(alkylseleno)allenes afforded (E)- and (Z)-1,3,4,6-tetraphenyl-3-hexene-1,5-diynes along with compounds derived from cyclic dimer of the allene or diselenide via radical pathway.     

Oxidation Behavior of Si–Nb–C–O Ceramics Prepared by the Pyrolysis of Methyltriethoxysilane Based Organic-Inorganic Hybrid Gel

The oxidative structural characterization of Si–Nb–C–O ceramic prepared by the heat-treatment of transition metal containing polymethylsilsesquioxane hybrid was investigated. The heating temperature for the pyrolysis of precursor hybrid gels strongly affected the oxidation behavior of the resultant ceramics. The hybrid gel pyrolyzed at 600C was rapidly oxidized, while the hybrid gel pyrolyzed at 1000C showed the higher resistance to oxidation. In the hybrid pyrolyzed at 600C, new Si–O–Nb oxygen-bridged heterometal bonds were formed after oxidation, which was confirmed by FT-IR spectra. On the other hand, silica and oxycarbide protective layer was formed on the oxidized surface of the hybrid heated at 1000C, as suggested by X-ray photoelectron spectroscopy (XPS). Raman spectra showed a large luminescence background, G and D bands before oxidation. After oxidation, however, the luminescence background disappeared and G band was more symmetric than that of non-oxidative product. This strongly suggested the predominant oxidation of radical and related unstable carbon species in the ceramics.     

Synthesis of J-111,347, a novel 1 beta-methylcarbapenem with broad-spectrum antibacterial activity

Synthesis of J-111,347 (1), a new 1 beta-methylcarbapenem with broad-spectrum antibacterial activity including that against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, was achieved via diastereoselective preparation of a side-chain thiol 3 from an optically active (R)-3,4-dihydroxybutanal 4.     

Pressure and isotope effects on the proton jump of the hydroxide ion at 25°C

The limiting molar conductances Λ⁰ of potassium deuteroxide KOD in D₂O and potassium hydroxide KOH in H₂O were determined at 25°C as a function of pressure to disclose the difference in the proton-jump mechanism between an OH^? (OD^?) and a H₃O⁺ (D₃O⁺) ion. The excess conductance of the OD^? ion in D₂O λ _E ^O (OD ^-), as estimated by the equation $$\lambda _E^O (OD^ - ) = \Lambda ^O (KOD/D_2 O) - \Lambda ^O (KCl/D_2 O)$$ increases a little with pressure as well as the excess conductance of the OH^? ion in H₂O $$\lambda _E^O (OH^ - ) = \Lambda ^O (KOH/H_2 O) - \Lambda ^O (KCl/H_2 O)$$ However, their rates of increase with pressure are much smaller than those of the excess deuteron and proton conductances, λ _E ^O (D ⁺) and λ _E ^O (H ⁺). With respect to the isotope effect on the excess conductance, λ _E ^O (OH ^-)/λ _E ^O (D ⁺) decreases with presure as in the case of λ _E ^O (H ⁺)/λ _E ^O (D ⁺), but the value of λ _E ^O (OH ^-)/λ _E ^O (OD ^-) itself is much larger than that of λ _E ^O (H ⁺)/λ _E ^O (D ⁺) at each pressure. These results are ascribed to the difference in the pre-rotation of water molecules, which is brought about by the difference in the intial orientation of the rotating water molecule adjacent to the OH^? (OD^?) or the H₃O⁺ (D₃O⁺) ion.     

Lipoproteins modulate growth and differentiation of cultured human epidermal keratinocytes

The effects of various lipoproteins on the growth and the differentiation of cultured normal human keratinocytes were investigated. Primary cultures of human epidermal keratinocytes were obtained from neonatal foreskin, and then added with lipoproteins, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL). Cell growth potential was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. VLDL and LDL enhanced keratinocytes growth and LDL receptor expression at the plasma membrane level. These effects were more remarkably observed in cells cultured with VLDL than in cells cultured with LDL. Apolipoprotein E (ApoE) was highly increased in VLDL treated cells. These results suggest that VLDL binds with high affinity to cell surface receptors and induces cell proliferation.