A Strategy for Neuraminidase Inhibitors Using Mechanism‐Based Labeling Information

A potent inhibitor for Vibrio cholerae neuraminidase (VCNA) was developed by using a novel two‐step strategy, a target amino acid validation using mechanism‐based labeling information, and a potent inhibitor search using a focused library. The labeling information suggested the hidden dynamics of a loop structure of VCNA, which can be a potential target of the novel inhibitor. A focused library composed of 187 compounds was prepared from a 9‐azide derivative of 2,3‐dehydro‐N‐acetylneuraminic acid (DANA) to interrupt the function of the loop of the labeled residues. Inhibitor 3c showed potent inhibition properties and was the strongest inhibitor with FANA, a N‐trifluoroacetyl derivative of DANA. Validation studies of the inhibitor with a detergent and a Lineweaver–Burk plot suggested that the 9‐substitution group would interact hydrophobically with the target loop moiety, adding a noncompetitive inhibition property to the DANA skeleton. This information enabled us to design compound 4 having the combined structure of 3c and FANA. Compound 4 showed the most potent inhibition (K_i=73 nM , mixed inhibition) of VCNA with high selectivity among the tested viral, bacterial, and mammal neuraminidases.     

Electronic conductivity of pure ceria

The electronic conductivity of pure ceria with two different impurity levels is examined by dc polarization technique based on the Hebb-Wagner ion blocking method. The impurity level for the ceria with 99.999% purity (5N-CeO₂) is about 1/100 of that with 99.9% purity (3N-CeO₂) as confirmed by the fluorescence intensity of impurities obtained by Raman spectroscopy. The electronic conductivity for the 5N-CeO₂ was measured at T = 973 K to 1173 K, and the results are essentially the same as those for the 3N-CeO₂. The electronic conductivity increases with decreasing of P(O₂) following slope values of − 1/4 to − 1/6. The − 1/4 dependent region becomes narrower for the 5N-CeO₂ than that for the 3N-CeO₂. For both types of ceria, the P(O₂) independent region appears in the same region of higher than 10^− 2 and 10^− 3 MPa at T = 1073 K and 973 K, respectively. Activation energies for the 5N-CeO₂ were 2.2 eV, 2.6 eV and 1.9 eV in P(O₂) dependent regions of − 1/6, − 1/4 and 0, respectively.     

Algebraic treatment of multi-step excitation processes in collective nuclei: (II). Electromagnetic excitation of collective nuclear states

Multi-step collective quadrupole excitations in nuclei are described using an algebraic method which does not require a coupled-channel calculation. Adiabatic effects are discussed. Applications to the axially-symmetric deformed rotor, anharmonic quadrupole vibrator, and γ-soft rotor, as well as to transitional nuclei, are presented using the consistent-Q formulation of the interacting boson model.     

Detection of arsenobetaine in human blood

Arsenobetaine was detected and quantified unambiguously in human plasma, serum and red blood cells by the combination of HPLC with ICP MS. Three different column conditions, i.e. two ionpair chromatographies for anionic (LC-1) and cationic (LC-2) compounds and gel-permeation chromatography (LC-3), were employed to confirm the assignment. Arsenobetaine was detected in every sample as a major component of the water-soluble arsenic compounds, with an increasing concentration in plasma < serum < blood cell fractions. It was the sole detectable arsenic compound in LC-1 and LC-2, while a broad peak corresponding to high-molecular-weight compounds was identified in addition to arsenobetaine in LC-3.     

New approach to unravel the structure–property relationship of methylcellulose

In the present paper we suggest a new concept to overcome some of the so far unsolved problems of the structure–property relationship of methylcellulose, the most important nonionic cellulose ether industrially produced in large scale. Not only from the viewpoint of scientific understanding, but also from that of the peculiar and application-determining behavior, the aggregation in aqueous solution and phase separation on heating are the most important questions. As a part of the concept, we had prepared amphiphilic block co-oligomers of tri-O-methylated and unmodified cello-oligosaccharides as structural models of typical sequences in methylcellulose chains. Now static and dynamic light scattering measurements and transmission electron microscopy (TEM) were carried out using solutions of the oligomers in water. Ellipsoidal particles with dimensions of about 50 nm for the semi-major axis and of circa 25 nm for the semi-minor one could be detected. These findings agree with the radii of gyration and the hydrodynamic radii, determined by static and dynamic light scattering. The data preliminary obtained demonstrate the strong aggregation tendency of block-like methylated cello-oligosaccharides.     

A light-controlled reversible DNA photoligation via carbazole-tethered 5-carboxyvinyluracil

We describe a light-controlled template-directed reversible DNA photoligation via carbazole-tethered 5-carboxyvinyluracil. Carbazole-tethered 5-carboxyvinyl-2'-deoxyuridine-containing oligodeoxynucleotide (ODN) can be ligated by irradiation at 366 nm in the presence of template ODN, and the ligated ODN can be split by irradiation at 366 nm in the absence of template ODN.     

Colloidal crystallization of colloidal silica modified with ferrocenyl group-contained polymers in organic solvents

Surface modification of colloidal silica with ferrocenyl-grafted polymer and colloidal crystallization of the particles in organic solvent were studied. Poly(methyl methacrylate-co-vinylferrocene)-grafted silica never formed colloidal crystals in polar solvent, such as acetone, acetonitrile, ethanol and N,N-dimethylformamide (DMF), while poly(methyl methacrylate-co-ferrocenyl acrylate)-grafted silica gave colloidal crystallization in DMF. The particles prepared by grafting of poly(N,N-dimethylacrylamide-co-vinylferrocene), with vinylferrocene (Vfc) mole fraction of 1/13 and 1/23, were observed to give the crystallization in ethanol and DMF over particle volume fraction of 0.058. Further, silica modified with copolymer of Vfc and N-vinyl-2-pyrrolidone, N-vinylcarbazole or N-isopropylacrylamide formed colloidal crystals in ethanol and DMF. Especially, poly(N-isopropylacrylamide-co-Vfc)-grafted silica, which was composed of the highest mole fraction of vinylferrocene, 1/3, afforded colloidal crystallization in ethanol over particle volume fraction of 0.053. Relatively high polar vinylferrocene copolymer grafting of silica resulted in colloidal polymerization in organic solvents.     

Systematic fragmentation patterns of archaeal intact polar lipids by high-performance liquid chromatography/electrospray ionization ion-trap mass spectrometry

Archaea are ubiquitous and abundant microorganisms on Earth that mediate key global biogeochemical cycles. The headgroup attached to the sn-1 position of the glycerol backbone and the ether-linked isoprenoid lipids are among the diagnostic traits that distinguish Archaea from Bacteria and Eukarya. Over the last 30 years, numerous archaeal lipids have been purified and described in pure cultures. Coupled high-performance liquid chromatography (HPLC) ion-trap mass spectrometry (ITMS) now enables the detection and rapid identification of intact polar lipids in relatively small and complex samples, revealing a wide range of archaeal lipids in natural environments. Although major structural groups have been identified, the lack of a systematic evaluation of MS/MS fragmentation patterns has hindered the characterization of several atypical components that are therefore considered as unknowns. Here, we examined mass spectra resulting from lipid analysis of natural microbial communities using HPLC/electrospray ionization (ESI)-ITMS(n), and depicted the systematics in MS(2) fragmentation of intact archaeal lipids. This report will be particularly useful for environmental scientists interested in a rapid and straightforward characterization of intact archaeal membrane lipids.