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991.
992.
Takashima-Hirano M Takashima T Katayama Y Wada Y Sugiyama Y Watanabe Y Doi H Suzuki M 《Bioorganic & medicinal chemistry》2011,19(9):2997-3004
Synthesis of [(11)C]celecoxib, a selective COX-2 inhibitor, and [(11)C]SC-62807, a major metabolite of celecoxib, were achieved and the potential of these PET probes for assessing the function of drug transporter in biliary excretion was evaluated. The synthesis of [(11)C]celecoxib was achieved in one-pot by reacting [(11)C]methyl iodide with an excess of the corresponding pinacol borate precursor using Pd(2)(dba)(3), P(o-tolyl)(3), and K(2)CO(3) (1:4:9) in DMF. The radiochemical yield of [(11)C]celecoxib was 63±23% (decay-corrected, based on [(11)C]CH(3)I) (n=7) with a specific radioactivity of 83±23GBq/μmol (n=7). The average time of synthesis from end of bombardment including formulation was 30min with >99% radiochemical purity. [(11)C]SC-62807 was synthesized from [(11)C]celecoxib by further rapid oxidation in the presence of excess KMnO(4) with microwave irradiation. The radiochemical yield of [(11)C]SC-62807 was 55±9% (n=3) (decay-corrected, based on [(11)C]celecoxib) with a specific radioactivity of 39±4GBq/μmol (n=3). The average time of synthesis from [(11)C]celecoxib including formulation was 20min and the radiochemical purity was >99%. PET studies in rats and the metabolite analyzes of [(11)C]celecoxib and [(11)C]SC-62807 showed largely different excretion processes, and consequently, [(11)C]SC-62807 was rapidly excreted via hepatobiliary excretion without further metabolism. [(11)C]SC-62807 was shown to have a high potential as a PET probe for evaluating drug transporter function in biliary excretion. 相似文献
993.
Hisashi Kato-Noguchi Ai Kobayashi Osamu Ohno Fukiko Kimura Yoshiharu Fujii Kiyotake Suenaga 《Journal of plant physiology》2014
The grass Brachiaria brizantha, native to eastern Africa, becomes naturalized and dominant quickly in the non-native areas. It was hypothesized that phytotoxic chemical interaction between this plant and native plants may play an important role in the invasion of B. brizantha. However, no potent phytotoxic substance has been reported in this species. Therefore, we investigated possible allelopathic activity and searched for phytotoxic substances with allelopathic activity in B. brizantha. An aqueous methanol extract of B. brizantha inhibited the growth of roots and shoots of garden cress (Lepidium sativum), lettuce (Lactuca sativa), timothy (Phleum pratense) and ryegrass (Lolium multiflorum) seedlings. The extract was purified by several chromatographic runs and three allelopathically active substances were isolated and identified by spectral analysis as (6R,9R)-3-oxo-α-ionol, (6R,9S)-3-oxo-α-ionol and 4-ketopinoresinol. (6R,9R)-3-Oxo-α-ionol and (6R,9S)-3-oxo-α-ionol inhibited root and shoot growth of garden cress at concentrations greater than 30 and 10 μM, respectively. The activity of (6R,9S)-3-oxo-α-ionol was 5.3- to 6.2-fold that of (6R,9R)-3-oxo-α-ionol. The stereochemistry of the hydroxyl group at position C-9 may be important for the inhibitory activities of those compounds. 4-Ketopinoresinol inhibited root and shoot growth of garden cress at concentrations greater than 30 μM. The growth inhibitory activity of (6R,9S)-3-oxo-α-ionol was the greatest and followed by 4-ketopinoresinol and (6R,9R)-3-oxo-α-ionol. These results suggest that those phytotoxic substances may contribute to the allelopathic effect caused by B. brizantha and may be involved in the invasion of B. brizantha. 相似文献
994.
Masaaki Toyoda Hiroyuki Kaji Hiromichi Sawaki Akira Togayachi Takashi Angata Hisashi Narimatsu Akihiko Kameyama 《Glycoconjugate journal》2016,33(6):917-926
Proteins carrying sulfated glycans (i.e., sulfated glycoproteins) are known to be associated with diseases, such as cancer, cystic fibrosis, and osteoarthritis. Sulfated glycoproteins, however, have not been isolated or characterized from complex biological samples due to lack of appropriate tools for their enrichment. Here, we describe a method to identify and characterize sulfated glycoproteins that are involved in chemical modifications to control the molecular charge of the peptides. In this method, acetohydrazidation of carboxyl groups was performed to accentuate the negative charge of the sulfate group, and Girard’s T modification of aspartic acid was performed to assist in protein identification by MS tagging. Using this approach, we identified and characterized the sulfated glycoproteins: Golgi membrane protein 1, insulin-like growth factor binding protein-like 1, and amyloid beta precursor-like protein 1 from H2171 cells, a small cell lung carcinoma cell line. These sulfated glycoproteins carry a complex-type N-glycan with a core fucose and 4′-O-sulfated LacdiNAc as the major glycan. 相似文献
995.
Mechanism for verification of mismatched and homoduplex DNAs by nucleotides‐bound MutS analyzed by molecular dynamics simulations 下载免费PDF全文
In order to understand how MutS recognizes mismatched DNA and induces the reaction of DNA repair using ATP, the dynamics of the complexes of MutS (bound to the ADP and ATP nucleotides, or not) and DNA (with mismatched and matched base‐pairs) were investigated using molecular dynamics simulations. As for DNA, the structure of the base‐pairs of the homoduplex DNA which interacted with the DNA recognition site of MutS was intermittently disturbed, indicating that the homoduplex DNA was unstable. As for MutS, the disordered loops in the ATPase domains, which are considered to be necessary for the induction of DNA repair, were close to (away from) the nucleotide‐binding sites in the ATPase domains when the nucleotides were (not) bound to MutS. This indicates that the ATPase domains changed their structural stability upon ATP binding using the disordered loop. Conformational analysis by principal component analysis showed that the nucleotide binding changed modes which have structurally solid ATPase domains and the large bending motion of the DNA from higher to lower frequencies. In the MutS–mismatched DNA complex bound to two nucleotides, the bending motion of the DNA at low frequency modes may play a role in triggering the formation of the sliding clamp for the following DNA‐repair reaction step. Moreover, MM‐PBSA/GBSA showed that the MutS–homoduplex DNA complex bound to two nucleotides was unstable because of the unfavorable interactions between MutS and DNA. This would trigger the ATP hydrolysis or separation of MutS and DNA to continue searching for mismatch base‐pairs. Proteins 2016; 84:1287–1303. © 2016 Wiley Periodicals, Inc. 相似文献
996.
Akira Harazono Tetsu Kobayashi Nana Kawasaki Satsuki Itoh Minoru Tada Noritaka Hashii Akiko Ishii Teruyo Arato Shigehiro Yanagihara Yuki Yagi Akiko Koga Yuriko Tsuda Mikiko Kimura Masashi Sakita Satoshi Kitamura Hideto Yamaguchi Hisashi Mimura Yoshimi Murata Yasuki Hamazume Takayuki Sato Teruhide Yamaguchi 《Biologicals》2011,39(3):171-180
The various monosaccharide composition analysis methods were evaluated as monosaccharide test for glycoprotein-based pharmaceuticals. Neutral and amino sugars were released by hydrolysis with 4–7 N trifluoroacetic acid. The monosaccharides were N-acetylated if necessary, and analyzed by high-performance liquid chromatography (HPLC) with fluorometric or UV detection after derivatization with 2-aminopyridine, ethyl 4-aminobenzoate, 2-aminobenzoic acid or 1-phenyl-3-methyl-5-pyrazolone, or high pH anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Sialic acids were released by mild acid hydrolysis or sialidase digestion, and analyzed by HPLC with fluorometric detection after derivatization with 1,2-diamino-4,5-methylenedioxybenzene, or HPAEC-PAD. These methods were verified for resolution, linearity, repeatability, and accuracy using a monosaccharide standard solution, a mixture of epoetin alfa and beta, and alteplase as models. It was confirmed that those methods were useful for ensuring the consistency of glycosylation. It is considered essential that the analytical conditions including desalting, selection of internal standards, release of monosaccharides, and gradient time course should be determined carefully to eliminate interference of sample matrix.Various HPLC-based monosaccharide analysis methods were evaluated as a carbohydrate test for glycoprotein pharmaceuticals by an inter-laboratory study. 相似文献
997.
The bembrid genusBembras Cuvier is reviewed. Five species,B. japonica Cuvier,B. adenensis Imamura & Knapp and three undescribed species, were assigned to the genus. Type species of the genus,Bembras japonica is redescribed on the basis of 36 specimens including the holotype, and three new species,B. macrolepis, B. longipinnis andB. megacephala, previously misidentified asB. japonicus, are also described on the basis of specimens collected from Australia and Indonesia.Bembras macrolepis differs from its congeners by having large body scales, a long pectoral fin with 17–19 rays and a dark blotch on slightly
upper portion to middle of margin, 14–15 anal-fin rays, small head and orbit, and caudal fin with a broad vertical dark band
near posterior margin.Bembras longipinnis is distinguished from other members of the genus by having a slightly long pectoral fin with 17–19 rays and lacking a small
black blotch near tip of upper rays, caudal fin with a large dark spot most intense in lower lobe, 1–2 gill rakers on upper
gill arch, 13–14 anal-fin rays, slightly elong ated head and small orbit.Bembras megacephala is characterized by the following combination of characters: caudal fin with several irregular narrow vertical dark bands,
small orbit, pectoral fin with 19–20 rays and lacking a small black blotch near tip of upper rays, head elongate, 2–4 gill
rakers on upper gill arch, 15 anal-fin rays and small body scales. A key separating the five species ofBembras is given. 相似文献
998.
GSH has multiple actions in physiological responses of plants, but the molecular mechanisms are not fully understood. GSH plays an important role in functional alteration of proteins by reversible covalent incorporation (glutathionylation) in vertebrate cells. To investigate the function of glutathionylation in plant cells, we examined glutathionylated proteins in the suspension-cultured cells of Arabidopsis using biotinylated GSH. Biotinylated GSH was incorporated into about 20 proteins. Two of these proteins were identified as the key enzymes for sugar metabolism, triose-phosphate isomerase (TPI) and putative plastidic aldolase. Recombinant TPI was inactivated by GSSG, and it was reactivated by GSH. The physiological roles of glutathionylation of TPI and aldolase in sugar metabolism are discussed. 相似文献
999.
Some symbiotic bacteria cause remarkable reproductive phenotypes like cytoplasmic incompatibility and male-killing in their host insects. Molecular and cellular mechanisms underlying these symbiont-induced reproductive pathologies are of great interest but poorly understood. In this study, Drosophila melanogaster and its native Spiroplasma symbiont strain MSRO were investigated as to how the host''s molecular, cellular and morphogenetic pathways are involved in the symbiont-induced male-killing during embryogenesis. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, anti-cleaved-Caspase-3 antibody staining, and apoptosis-deficient mutant analysis unequivocally demonstrated that the host''s apoptotic pathway is involved in Spiroplasma-induced male-specific embryonic cell death. Double-staining with TUNEL and an antibody recognizing epidermal marker showed that embryonic epithelium is the main target of Spiroplasma-induced male-specific apoptosis. Immunostaining with antibodies against markers of differentiated and precursor neural cells visualized severe neural defects specifically in Spiroplasma-infected male embryos as reported in previous studies. However, few TUNEL signals were detected in the degenerate nervous tissues of male embryos, and the Spiroplasma-induced neural defects in male embryos were not suppressed in an apoptosis-deficient host mutant. These results suggest the possibility that the apoptosis-dependent epidermal cell death and the apoptosis-independent neural malformation may represent different mechanisms underlying the Spiroplasma-induced male-killing. Despite the male-specific progressive embryonic abnormality, Spiroplasma titers remained almost constant throughout the observed stages of embryonic development and across male and female embryos. Strikingly, a few Spiroplasma-infected embryos exhibited gynandromorphism, wherein apoptotic cell death was restricted to male cells. These observations suggest that neither quantity nor proliferation of Spiroplasma cells but some Spiroplasma-derived factor(s) may be responsible for the expression of the male-killing phenotype. 相似文献
1000.