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131.
Youichi Kawakita Masaki Seto Tomohiro Ohashi Toshiya Tamura Tadashi Yusa Hiroshi Miki Hidehisa Iwata Hidenori Kamiguchi Toshimasa Tanaka Satoshi Sogabe Yoshikazu Ohta Tomoyasu Ishikawa 《Bioorganic & medicinal chemistry》2013,21(8):2250-2261
A novel 7,6 fused bicyclic scaffold, pyrimido[4,5-b]azepine was designed to fit into the ATP binding site of the HER2/EGFR proteins. The synthesis of this scaffold was accomplished by an intramolecular Claisen-type condensation. As the results of optimization lead us to 4-anilino and 6-functional groups, we discovered 6-substituted amide derivative 19b, which has a 1-benzothiophen-4-yloxy group attached to the 4-anilino group. An X-ray co-crystal structure of 19b with EGFR demonstrated that the N-1 and N-3 nitrogens of the pyrimido[4,5-b]azepine scaffold make hydrogen-bonding interactions with the main chain NH of Met793 and the side chain of Thr854 via a water-mediated hydrogen bond network, respectively. In addition, the NH proton at the 9-position makes an additional hydrogen bond with the carbonyl group of Met793, as we expected. Compound 19b revealed potent HER2/EGFR kinase (IC50: 24/36 nM) and BT474 cell growth (GI50: 18 nM) inhibitory activities based on its pseudo-irreversible (PI) profile. 相似文献
132.
Shymaa Enany Yutaka Yoshida Sameh Magdeldin Xu Bo Ying Zhang Mohamed Enany Tadashi Yamamoto 《Microbiological research》2013,168(8):504-511
Two-dimensional electrophoresis (2DE) combined with mass spectrometry was used to characterize the exo-proteome secreted by two strains (ER13 and ER21) representing community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) belonging to clonal complex 80 (CC80). Common spots were detected between the 2 gels using the Progenesis SameSpots software. Two hundred and fifty-one and 312 spots from the exo-proteome of ER13 and ER21 were resolved, respectively. 2DE overlap comparison showed that 59 spots were shared. LC–MS/MS analysis identified 57 proteins from these spots comprising about 21% extracellular, 48% cytoplasmic, 2% cytoplasmic membrane, 2% cell wall, and 26% with unknown localization. The identified proteins were classified with respect to their Gene Ontology (GO) annotation as ~24% virulence determinants and toxins, ~17% involved in carbohydrate metabolism, ~14% involved in environmental stress, and ~12% associated with cell division. The identification of the enterotoxin B from the exo-products of both strains used in our study, as belonging to CC80 was interesting. 相似文献
133.
134.
Tadashi Shimamura Satoe Iijima Mitsuhiro Hirayama Masato Iwashita Shigeru Akiyama Yuichi Takaku Sakae Yumoto 《Journal of trace elements in medicine and biology》2013,27(4):286-294
The concentrations of 22 major and trace elements in livers from rats aging from 5 to 113 weeks old were determined. The rats investigated were the same rats previously reported with respect to 29 elements in bones (femur) and 26 elements in kidneys. The samples were decomposed with high-purity nitric acid and hydrogen peroxide. Seven elements (Na, Mg, P, K, Ca, Fe and Zn) were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES), and 15 elements (Mn, Co, Cu, As, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Ba, Pb and Bi) were determined by inductively coupled plasma mass spectrometry (ICP-MS). Analysis of variance (ANOVA) for age variations indicated that the concentrations of many elements, such as Mg, P, K, Mn, Fe, Cu, Zn, Sr, Mo and Cd, were almost constant across the ages of the rats with the exception of 5 weeks old (p > 0.05). Arsenic, Pb and Bi showed significant increasing trends, while Na and Co showed decreasing trends (p < 0.01). Selenium showed a decreasing trend except at the initial stage of 5–9 weeks old. Calcium, Rb, Sn, Sb, Cs and Ba showed significant age-related variations, but their patterns were not monotonic. The liver clearly contrasts with the kidneys, in which many elements showed significant age-related variations with increasing trends. The concentration ranges of Mg, P, K, Mn, Cu, Zn, and Mo were controlled within 15% across all ages of rats. The homeostasis of the aforementioned elements may be well established in the liver. The toxic elements, such as Cd, Pb and Bi, showed a narrow concentration range among age-matched rats. 相似文献
135.
Jiro Arima Yoshitaka Isoda Tadashi Hatanaka Nobuhiro Mori 《World journal of microbiology & biotechnology》2013,29(5):899-906
N-Acyl-d-amino acid amidohydrolases (d-aminoacylases) are often used as tools for the optical resolution of d-amino acids, which are important products with applications in industries related to medicine and cosmetics. For this study, genes encoding d-aminoacylase were cloned from the genomes of Streptomyces spp. using sequence-based screening. They were expressed by Escherichia coli and Streptomyces lividans. Almost all of the cell-free extracts exhibit hydrolytic activity toward N-acetyl-(Ac-)d-Phe (0.05–6.32 μmol min?1 mg?1) under conditions without CoCl2. Addition of 1 mM CoCl2 enhanced their activity. Among them, the highest activity was observed from cell-free extracts prepared from S. lividans that possess the d-aminoacylase gene of Streptomyces sp. 64E6 (specific activities were, respectively, 7.34 and 9.31 μmol min?1 mg?1 for N-Ac-d-Phe and N-Ac-d-Met hydrolysis). Furthermore, when using glycerol as a carbon source for cultivation, the recombinant enzyme from Streptomyces sp. 64E6 was produced in 4.2-fold greater quantities by S. lividans than when using glucose. d-Aminoacylase from Streptomyces sp. 64E6 showed optimum at pH 8.0–9.0. It was stable at pH 5.5–9.0 up to 30 °C. The enzyme hydrolyzed various N-acetyl-d-amino acids that have hydrophobic side chains. In addition, the activity toward N-chloroacetyl-d-Phe was 2.1-fold higher than that toward N-Ac-d-Phe, indicating that the structure of N-acylated portion of substrate altered the activity. 相似文献
136.
Nitrogenase catalyzes not only the reduction of N2 to NH3 but also the reduction of C2H2 to C2H4 and H+ ion to H2 gas, etc. The detailed mechanism of the nitrogenase reaction is not clear. We have prepared monoclonal antibodies against Component I nitrogenase of A. vinelandii and examined the effects of antibodies on the nitrogenase reactions. A monoclonal antibody designated MA-1 inhibited C2H2 reduction activity strongly but did not inhibit H2 evolution activity. MA-2, on the contrary, inhibited only H2 evolution activity. MA-8 inhibited both C2H2 reduction and H2 evolution activity to the same extent. 相似文献
137.
Tadashi Sudo Hideo Nagayama Kinjiro Tamari 《Bioscience, biotechnology, and biochemistry》2013,77(11):2535-2542
In order to explain the difference in extracellular cellulase activities (C1 and Cx enzyme activities) among various strains of P. oryzae, the elution patterns from the column were compared among various strains, following each step of the partial purification.The crude enzymes, prepared by ammonium sulfate fractionation (0.2~0.8 sat.) from the culture filtrates, which were obtained from various strains of P. oryzae cultured on rice plant powder as the carbon source, were fractionated by DEAE-Sephadex A–50 chromatography into two components; the passing-through fraction (I) and the fraction (II) adsorbed and eluted from the column with 0.5 M NaCl The percentage of the enzyme activity (Cx enzyme activity) in fraction I to that of the crude extract was found to vary chracteristically according to the strain, and the variation was in a good correlation to that of the extracellular cellulase activities.Fractions I and II were then separated by Sephadex G–100 into two (peaks a and b) and at least five (peaks c, d, e, f and g) components, respectively. The activities in peaks a, b and g were found to vary according to the strain, while those of peaks c and e were common among various strains.The cell wall fraction prepared from C–3 strain, which was previously shown to be low in enzyme activity and thus out of the correlation between the degree of pathogenicity and extracellular cellulase activity, was found to exhibit higher cellulase activities (C1 and Cx enzyme activities) than those of other strains examined. Thus, the low extracellular cellulase activity in the case of C–3 strain was suggested to be due to the abnormality in the mechanism of enzyme excretion. 相似文献
138.
The transxylosylation reaction products of β-xylosidase-1, excreted by Penicillium wortmanni IFO 7237 using β-(1→4)-xylobiose as substrate, have been separated by chromatography on activated charcoal into four fractions, designated as P-1, P-2, P-3, and P-4, respectively. They were further purified by preparative paper chromatography. The characterization and structural analysis were done by measurement of the degree of polymerization (DP) and specific rotation followed by methylation analysis. Moreover, the enzymatic structural analysis of transxylosylation products, with high performance liquid chromatography (HPLC), allowed the confirmation of each structure. The first product, P-1, was β-(1→3)-xylobiose and the second, P-2, was β-(1→4)-xylotriose, but, P-3 was O-β-d-xylopyranosyl-(1→3)-O-β-d-xylopyranosyl-(1→4)-d-xylopyranose or isomeric xylo-triose and P-4 was assumed to be O-β-d-xylopyranosyl-(1→4)-[O-β-d-xylopyranosyl-(1→3)]-O-β-d-xylopyranosyl-(1→4)-d-xylopyranose. 相似文献
139.
140.
The reaction catalyzed by crystalline yeast phosphoglyceric acid mutase is inhibited by the substrate (d-2-phosphoglyceric acid). In order to elucidate the mechanism of this substrate inhibition, detailed investigations have been performed. It is proved that the substrate inhibition in this enzyme reaction is caused by the facts that the coenzyme-binding site on the enzyme is covered by the substrate and the combination of the coenzyme with the enzyme is interfered by the substrate. Consequently, it is concluded that the substrate is a competitive inhibitor of the coenzyme. 相似文献