Synthetic Studies on Sialoglycoconjugates 49: Novel Disaccharides and Lactams Composed of Sialic Acid and 1-Deoxynojirimycin-Potential for Biomedical Application

Abstract

Sialic acid-containing glycoconjugates participate in a variety of biological functions on cell surfaces, not only serving as receptors for hormones, viruses and bacteria but also as mediators in cell growth, differentiation, adhesion, oncogenesis and so on. For example, influenza virus^1,2 and tripanosoma cruzi ^3,4 recognize sialic acid in the time of infection to animal cells. Recently, the sialyl-Le^x (sLe^x) and sialyl-Le^a (sLe^a) carbohydrate epitopes have been highlighted as the ligands for selectins, a family of cell adhesion molecules involved in leukocyte traffic^5,6 and tumor metastasis.⁷ 1-Deoxynojirimycin (DNJ) and related compounds are well known⁸ as the potent inhibitors of a-glycosidases and glycoprotein-processing enzymes. Some of the Nsubstituted DNJ derivatives have been noted as antidiabetic and anti-HIV agents.     

Staphylococcus aureus Penicillin‐Binding Protein 2 Can Use Depsi‐Lipid II Derived from Vancomycin‐Resistant Strains for Cell Wall Synthesis

Vancomycin‐resistant Staphylococcus aureus (S. aureus) (VRSA) uses depsipeptide‐containing modified cell‐wall precursors for the biosynthesis of peptidoglycan. Transglycosylase is responsible for the polymerization of the peptidoglycan, and the penicillin‐binding protein 2 (PBP2) plays a major role in the polymerization among several transglycosylases of wild‐type S. aureus. However, it is unclear whether VRSA processes the depsipeptide‐containing peptidoglycan precursor by using PBP2. Here, we describe the total synthesis of depsi‐lipid I, a cell‐wall precursor of VRSA. By using this chemistry, we prepared a depsi‐lipid II analogue as substrate for a cell‐free transglycosylation system. The reconstituted system revealed that the PBP2 of S. aureus is able to process a depsi‐lipid II intermediate as efficiently as its normal substrate. Moreover, the system was successfully used to demonstrate the difference in the mode of action of the two antibiotics moenomycin and vancomycin.     

Brain site-specific proteome changes in aging-related dementia

This study is aimed at gaining insights into the brain site-specific proteomic senescence signature while comparing physiologically aged brains with aging-related dementia brains (for example, Alzheimer''s disease (AD)). Our study of proteomic differences within the hippocampus (Hp), parietal cortex (pCx) and cerebellum (Cb) could provide conceptual insights into the molecular mechanisms involved in aging-related neurodegeneration. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) brain site-specific proteomic strategy, we identified 950 proteins in the Hp, pCx and Cb of AD brains. Of these proteins, 31 were significantly altered. Most of the differentially regulated proteins are involved in molecular transport, nervous system development, synaptic plasticity and apoptosis. Particularly, proteins such as Gelsolin (GSN), Tenascin-R (TNR) and AHNAK could potentially act as novel biomarkers of aging-related neurodegeneration. Importantly, our Ingenuity Pathway Analysis (IPA)-based network analysis further revealed ubiquitin C (UBC) as a pivotal protein to interact with diverse AD-associated pathophysiological molecular factors and suggests the reduced ubiquitin proteasome degradation system (UPS) as one of the causative factors of AD.     

Photodissociation of multilayered trimethylaluminum adsorbed on a cryogenic substrate: A time-of-flight mass-spectrometric study

Photodissociation of trimethylaluminum [Al(CH₃)₃] adsorbed on a silica (SiO₂) substrate at 110 K has been studied by multiphoton ionization time-of-flight mass spectrometry. Translational energy distributions of aluminum and AlCH₃ fragments can be fitted with a composition of two Maxwell–Boltzmann distributions. The two components are attributed to different environments of photodissociating parent molecules in the multilayer.     

Laser photochemistry of organometallic compounds related to applications in microelectronics

Photochemistry of organometallic compounds achieves a marriage of a rich variety of organometallic chemistry and the full potential of electronically excited states of molecules. The application of lasers as light sources adds a great many new features to these studies, which cannot be attained by other means, because lasers provide light of such a high quality, e.g. a high-intensity, energetic (i.e. wavelength) purity, a high degree of coherence, and a high spatial and temporal resolution. Laser photochemistry of organometallic compounds, such as laser photochemical vapor deposition (LPCVD), laser ablation, and photochemical dry etching, forms the basis of many important industrial processes which sustain the present-day microelectronics industries. Lasers are used not only to photodissociate organometallic molecules, but to monitor the reaction steps by probing the starting material, chemical intermediate, or final product by many laser-based spectroscopic methods. Although it is a very young area of science (the first laser was operated in 1960), this research area is now really ebullient, as a result of strong interest from both the fundamental and the practical sides. Laser photochemistry of organometallic compounds extends a wide and fertile research frontier, full of challenge and novel possibilities. In the present review, the present status of laser (ultraviolet and visible) photochemistry of organometallic compounds related to these industrial applications is briefly reviewed, with special emphasis on the basic studies of the relevant photochemistry and their relationship to photochemical processes on solid surfaces.     

Estimation of the parameters in the Kirkwood-Buff theory of solution using Percus-Yevick fluid mixtures

Parameters G _ij in the Kirkwood-Buff theory of solution were calculated for binary fluid mixtures of Lennard-Jones (LJ) 6–12 molecules by using the Percus-Yevick theory. Calculations were carried out for various parameters in the LJ potential. Under the Lorentz-Berthelot rules, G ₁₁ and/or G ₂₂ -composition curves do not show a maximum for any parameters in the LJ potential. When the intermolecular interaction between different species becomes much weaker than that expected from the Berthelot rule, G ₁₁ and G ₂₂ show a maximum and G ₁₂ a minimum. The pressure effect on G _ij was examined and calculations at constant pressure were also carried out. G _ij is almost independent of the pressure when the ratio of the molecular volume of two components is in the range 1.0 to 2.5. Comparison was made between experimental and calculated G _ij for cyclohexane-2,3-dimethylbutane and acetonitrile-toluene systems. For the latter system, the quantitative agreement between the calculated and experimental could not be obtained but showed that the characteristics of G _ij -composition curves can be explained qualitatively by using the PY theory.Adjunct Associate Professor of Institute for Molecular Science (April 1982–March 1984)     

A deformation of flat conformal structures

We consider deformations of flat conformal structures from a viewpoint of connected sum decomposition of conformally flat manifolds.

     

Determination of diphenylarsinic acid and phenylarsonic acid,the degradation products of organoarsenic chemical warfare agents,in well water by HPLC–ICP‐MS

Diphenylarsinic acid (DPAA) and phenylarsonic acid (PAA), which were degradation products of organoarsenic chemical warfare agents used as sternutatory gas, were detected in the well water at Kamisu, Ibaraki Prefecture, Japan. The standard material of DPAA was synthesized with aqueous arsenic acid and phenylhydrazine in order to determine organic arsenic compounds in well water. The DPAA showed a protonated ion at m/z 263 [M + H]⁺ and a loss of H₂O ion at m/z 245 [M + H ? H₂O]⁺ from protonated ion by the electrospray ionization time‐of‐flight mass spectrometry. The quantitative analysis of DPAA and PAA was performed by high‐performance liquid chromatography inductively coupled plasma mass spectrometry and the system worked well for limpid liquid samples such as well water. Copyright © 2005 John Wiley & Sons, Ltd.     

Penning ionization electron spectroscopy and photo-electron spectroscopy of molecular solids. II. Ammonia and water

The Penning ionization electron spectra (PIES) and ultraviolet photoelectron spectra (UPS) of ammonia and water molecules condensed on a cold metal substrate have been measured using thermal He*(2³S, 2¹S) metastable atoms and He(I) (58.4 nm) photons. The shifts of the observed positions of the PIES peaks relative to those of the UPS peaks in the condensed phase are roughly equal to the corresponding shifts in the gas phase. The relative intensities of the 3a₁ and 1e orbital peaks are reversed in the PIES and UPS for both gaseous and condensed ammonia; the origin of this reversal is interpreted as the difference between the interactions with metastable atoms and photons. On the other hand, the relative intensities of the 3a₁ orbital peak in the PIES and UPS for condensed water decrease as compared to the gas-phase spectra. This implies participation of the 3a₁ orbital of water in the hydrogen bonding.