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81.
Masao Ohashi Takuji Oyama Endy Widya Putranto Tsuyoshi Waku Hiromi Nobusada Ken Kataoka Kenji Matsuno Masakazu Yashiro Kosuke Morikawa Nam-ho Huh Hiroyuki Miyachi 《Bioorganic & medicinal chemistry》2013,21(8):2319-2332
In the continuing study directed toward the development of peroxisome proliferator-activated receptor gamma (hPPARγ) agonist, we attempted to improve the water solubility of our previously developed hPPARγ-selective agonist 3, which is insufficiently soluble for practical use, by employing two strategies: introducing substituents to reduce its molecular planarity and decreasing its hydrophobicity via replacement of the adamantyl group with a heteroaromatic ring. The first approach proved ineffective, but the second was productive. Here, we report the design and synthesis of a series of α-benzyl phenylpropanoic acid-type hPPARγ partial agonists with improved aqueous solubility. Among them, we selected (R)-7j, which activates hPPARγ to the extent of about 65% of the maximum observed with a full agonist, for further evaluation. The ligand-binding mode and the reason for the partial-agonistic activity are discussed based on X-ray-determined structure of the complex of hPPARγ ligand-binding domain (LBD) and (R)-7j with previously reported ligand-LDB structures. Preliminal apoptotic effect of (R)-7j against human scirrhous gastric cancer cell line OCUM-2MD3 is also described. 相似文献
82.
Masaki Wakasugi Hiroaki Gouda Tomoyasu Hirose Akihiro Sugawara Tsuyoshi Yamamoto Kazuro Shiomi Toshiaki Sunazuka Satoshi Ōmura Shuichi Hirono 《Bioorganic & medicinal chemistry》2013,21(11):3214-3220
Human acidic mammalian chitinase (hAMCase) was recently shown to be involved in the development of asthma, suggesting a possible application for hAMCase inhibitors as novel therapeutic agents for asthma. We therefore initiated drug discovery research into hAMCase using a combination of in silico methodologies and a hAMCase assay system. We first selected 23 candidate hAMCase inhibitors from a database of four million compounds using a multistep screening system combining Tripos Topomer Search technology, a docking calculation and two-dimensional molecular similarity analysis. We then measured hAMCase inhibitory activity of the selected compounds and identified seven compounds with IC50 values ?100 μM. A model describing the binding modes of these hit compounds to hAMCase was constructed, and we discuss the structure–activity relationships of the compounds we identified, suggested by the model and the actual inhibitory activities of the compounds. 相似文献
83.
Tsuyoshi Fujitani 《Bioscience, biotechnology, and biochemistry》2013,77(11):762-766
It was found that the intercellular space of centrifuged sake yeast cultured in anaerobic medium is 0.263 ml/g, which is larger than that of bakers’ yeast. On the preparation of the calibration curve, this centrifuged sake yeast wras used as standard substance.The diameters of the majority of cells were included in a range of 3~8µ during the whole course of cultural development. A similar distribution was found on the cells cultured in an abnormal medium. From these results, clearly, the turbidimetric method for the evaluation of the cell amount of yeast cultured anaerobically is unaffected by the cultural conditions. 相似文献
84.
85.
Tsuyoshi Sugio Shinji Tanijiri Kyoko Fukuda Kenji Yamaryo Kenji Inagaki Tatsuo Tano 《Bioscience, biotechnology, and biochemistry》2013,77(8):2229-2236
An obligate chemolithoautotroph, Thiobacillus ferrooxidans API 9–3, could utilize amino acids, other than glycine, methionine and phenylalanine, as a sole source of nitrogen. However, both the growth rate and growth yield were lower than those in Fe2+-NH4 -salts medium, suggesting that the ammonium ion was a superior nitrogen source for the strain compared to amino acids. Methionine and phenylalanine strongly inhibited the cell growth on Fe2+-NH4-salts medium at 10 mm. [14C]Glycine could not be taken up into the cells, and this meant the strain could not use glycine as a sole source of nitrogen. The uptake of [14C]leucine into the cells was dependent on the presence of Fe2 +. When the strain was cultured on Fe2 + - leucine (lOmm)-salts medium lacking an inorganic nitrogen source for 5 days at 30°C, 83.5% and 16.5% of the cellular carbon were derived from carbon dioxide and leucine, respectively, indicating that carbon dioxide was a superior carbon source for the bacterium compared to leucine. The ammonium ion did not inhibit the utilization of leucine for cellular carbon. Leucine uptake was markedly inhibited by inhibitors of protein synthesis, such as chloramphenicol (94.3% at 1 mm), streptomycin (57.2% at 5mm) and rifampin (77.2% at 0.1 mm), respectively. Carbon dioxide uptake was also completely inhibited by chloramphenicol at 4mm. These results suggest that the transport of both amino acids and carbon dioxide into the cells was dependent on protein synthesis. 相似文献
86.
Tsuyoshi Fujiwara Shinzo Izumi Patrick J. Brennan 《Bioscience, biotechnology, and biochemistry》2013,77(8):2301-2308
The disaccharide, 2,3-di-O-methyl-4-O-(3,6-di-O-methyl-β-d-glucopyranosyl)-l-rhamno-pyranose, the distal segment of phenolic glycolipid I, that is a specific antigen from Mycobacterium leprae, and some related disaccharides were synthesised as the glycosides of methyl 3-(p-hydroxyphenyl)propionate. The methyl 3-(p-hydroxyphenyl)propionate was coupled with 2,3,4-tri-O-acetyl-l-rhamnosyl bromide, deacetylated, acetonated, coupled with 2,4,6-tri-O-acetyl-3-O-methyl-d-glucosyl bromide, and converted into a variety of p-(2-methoxycarbonylethyl)phenyl 4-O-(3,6-di-O-methyl-d-glucopyranosyl)-containing disaccharides that are amenable to ready conjugation with protein carriers, thereby providing neo-glycoconjugates for the specific serodiagnosis of leprosy. 相似文献
87.
Kazutami Imai Tsuyoshi Sugio Takanori Tsuchida Tatsuo Tano 《Bioscience, biotechnology, and biochemistry》2013,77(7):1349-1354
Effect of heavy metal ions on the growth and the iron-oxidizing activity of Thiobacillus ferrooxidans were investigated.Cupric, zinc, cadmium, and chromium ions had no effect on the growth and the iron-oxidizing activity of cell suspensions or cell-free extracts of the bacterium in high concentrations (10?3~10?2M). Lead ion delayed the start of the growth slightly in 10?3 M, but it did not inhibit the iron-oxidizing activity of the cells in the concentration. Tin and molybdenum oxide ions inhibited both of them in the concentration above 10?3 M.Mercuric mercurous, and silver ions had the most harmful effect. In the concentration of 10?3 .M, each of the cations inhibited almost completely both the growth and the iron-oxidizing activity of the cells.In the experiments with cell-free extracts it was observed that the activity of cytochrome oxidase (cytochrome a597) operating in the iron-oxidizing system of the bacterium was specifically inhibited with mercuric ion in the concentration above 5 × 10?4 M. 相似文献
88.
Tsuyoshi Fujitani 《Bioscience, biotechnology, and biochemistry》2013,77(9):925-930
The critical concentrations of minerals in a growing medium for maximum fermentation of yeast were as follows: P, 1 mmol/1; Mg, 0.2 mmol/1; and K, 1~2 mmol/1. These values are lower than those for the saturation of the cells with each mineral. The order of the concentration for maximum fermentation (K>P>Mg) is in agreement with that for yeast growth.Only a small amount of mineral salt was required to increase the fermentative activity. Very small increase of fermentative activity was observed when the starved yeast was enriched with corresponding minerals by incubating cells with the mineral salt and glucose. 相似文献
89.
Yoshiki Tani Koichi Ogata Masao Ukita Tsuyoshi Nakamatsu Yoshikazu Izumi 《Bioscience, biotechnology, and biochemistry》2013,77(2):173-197
Escherichia freundii alkaline phosphatase was found in a membrane fraction and was purified by procedures involving spheroplast formation with lysozyme and EDTA, and DEAE-cellulose and Sephadex G-150 column chromatographies. Then this enzyme along with other phosphatases was investigated on the ability to transfer the phosphoryl group from p-nitrophenyl phosphate to pyridoxine. It was found that the ability of the transphosphorylation varied with these phosphatases. The transphosphorylation to hydroxy compounds such as alcohols, sugars and nucleosides was also compared. Escherichia freundii acid phosphatase showed the highest activity of transphosphorylation among phosphatases tested. The mechanism of transphosphorylation was discussed.An enzyme, pyridoxamine 5′-phosphate transaminase, was purified from the cell-free extract of Clostridium kainantoi. The purification procedures involved ammonium sulfate fractionation, protamine sulfate treatment and, DEAE-cellulose, hydroxylapatite, DEAE-Sephadex and Sephadex G-200 column chromatographies. The purified enzyme, which had approximately 2700-fold higher specific activity over the original extract, showed a single schlieren pattern in the ultracentrifuge. From the spectral analysis, it seemed that pyridoxamine 5′-phosphate transaminase did not contain pyridoxal 5′-phosphate as a prosthetic group. It was recognized that the transamination was accelerated by the addition of amino acid and was inhibited by diisopropyl phosphofluoride. Glutamic acid formed in the reaction was identified to be a D-isomer. A study on the substrate specificity showed that the enzyme might be possible to be specific for pyridoxamine 5′-phosphate.The extracellular formation of vitamin B6 was searched in marine and terrestrial microorganisms. Two bacterial strains were selected and were identified as Vibrio and Flavobacterium, respectively. Marine microorganisms showed the considerable formation of vitamin B6 and the presence of vitamin B6 in sea water was also recognized. The cultural and reaction conditions for vitamin B6 formation by these strains were investigated. Glycerol was commonly the most effective compound on vitamin B6 formation among the compounds tested. It was suggested that both bacteria did not have the control system on vitamin B6 biosynthesis by the amount of possible end products. 相似文献
90.
Haruya Takahashi Kosuke Kamakari Hideyuki Suzuki Shinsuke Mohri Tsuyoshi Goto Nobuyuki Takahashi 《Bioscience, biotechnology, and biochemistry》2013,77(10):1761-1764
We previously reported that the two peroxisome proliferator-activated receptor-α agonists, 9- and 13-oxo-octadecadienoic acids (oxo-ODAs), were found in the tomato fruit. However, their localization remains unknown. Herein, we showed that oxo-ODAs localize primarily in the fruit peel and their amount increases after the homogenization of the tomato fruit. 相似文献