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81.
Gökçen Eren Serdar Ünlü Maria-Teresa Nuñez Luis Labeaga Francisco Ledo Antonio Entrena Erden Banoğlu Gabriele Costantino M. Fethi Şahin 《Bioorganic & medicinal chemistry》2010,18(17):6367-6376
Three novel series of diaryl heterocyclic derivatives bearing the 2-oxo-5H-furan, 2-oxo-3H-1,3-oxazole, and 1H-pyrazole moieties as the central heterocyclic ring were synthesized and their in vitro inhibitory activities on COX-1 and COX-2 isoforms were evaluated using a purified enzyme assay. The 2-oxo-5H-furan derivative 6b was identified as potent COX inhibitor with selectivity toward COX-1 (COX-1 IC50 = 0.061 μM and COX-2 IC50 = 0.325 μM; selectivity index (SI) = 0.19). Among the 1H-pyrazole derivatives, 11b was found to be a potent COX-2 inhibitor, about 38 times more potent than Rofecoxib (COX-2 IC50 = 0.011 μM and 0.398 μM, respectively), but showed no selectivity for COX-2 isoform. Compound 11c demonstrated strong and selective COX-2 inhibitory activity (COX-1 IC50 = 1 μM, COX-2 IC50 = 0.011 μM; SI = ~92). Molecular docking studies of compounds 6b and 11b–d into the binding sites of COX-1 and COX-2 allowed to shed light on the binding mode of these novel COX inhibitors. 相似文献
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Multiple traits of agronomic importance in transgenic indica rice plants: analysis of transgene integration patterns,expression levels and stability 总被引:16,自引:0,他引:16
Maqbool Shahina Bano Christou Paul 《Molecular breeding : new strategies in plant improvement》1999,5(5):471-480
We cotransformed indica rice (Oryza sativa L. cvs. Basmati 370 and M7) with three plasmids, carrying a total of four genes, by particle bombardment. The Bacillus thuringiensis (Bt) -endotoxin genes cry1Ac and cry2A were carried on separate vectors, while the gna (snowdrop lectin) and hpt (hygromycin phosphotransferase) genes were linked on the same, cointegrate vector. We evaluated the molecular and expression profiles of 29 independently derived transgenic lines over two generations. The gna and hpt genes cointegrated with a frequency of 100% as expected. Furthermore, 60% of the transgenic plants carried all four genes. Southern blot analysis showed that transgene copy number ranged from 1 to 15. We used western blots to determine protein expression levels in R0 and R1 plants. We observed wide variation in the expression levels of the nonselected transgenes among independently-derived lines, but expression levels within lines derived from the same clone were similar. Consistent with previous reports, we observed no correlation between transgene copy number and the level or stability of protein expression. We show that the introduction of multiple agronomically valuable genes into the rice genome by cotransformation is a practical strategy for engineering elite rice varieties. 相似文献
85.
Post fish oil(n-3 fatty acids) treatment (5mg/kg/day for 12 days) was effective in bringing the reversal of tobramycin (160mg/kg/day,ip for 12 days) induced nephrotoxicity in albino rats as was evident by normal urea, creatinine, cholesterol and inorganic phosphate levels in the serum of the treatment group compared with group receiving tobramycin only. The return of normal levels of alkaline and acid phosphatase in kidney homogenates of post fish oil treatment group also indicated the beneficial effect of dietary n-3 fatty acids(fish oil) more than n-6 fatty acids(olive oil).The results suggest that oral supplements of dietary n-3 fatty acids (fish oil) for nearly two weeks after tobramycin exposure is more beneficial than n-6 fatty acids (olive oil) as it results in reversal of nephrotoxicity induced by tobramycin. 相似文献
86.
Crystallins are recognized as one of the long-lived proteins of lens tissue that might serve as the target for several posttranslational modifications leading to cataract development. We have studied several such sites present in the human gamma-crystallins based either on PROSITE pattern search results or earlier experimental evidences. Their probabilities were examined on the basis of the database analysis of the gamma-crystallin sequences and on their specific locations in the constructed homology models. An N-glycosylation site in human gammaD-crystallin and several phosphorylation sites in all four human gamma-crystallins were predicted by the PROSITE search. Some of these sites were found to be strongly conserved in the gamma-crystallin sequences from different sources. An extensive analysis of these sites was performed to predict their probabilities as potential sites for protein modifications. Glycation studies were performed separately by attaching sugars to the human gammaB-crystallin model, and the effect of binding was analyzed. The studies showed that the major effect of alphaD-glucose (alphaD-G) and alphaD-glucose-6-phosphate (alphaD-G6P) binding was the disruption of charges not only at the surface but also within the molecule. Only a minor alteration in the distances of sulfhydryl groups of cysteines and on their positions in the three-dimensional models were observed, leading us to assume that glycation alone is not responsible for intra- and intermolecular disulfide bond formation. 相似文献
87.
Partial sequences of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) (EC 4.1.1.39) genes were retrieved from samples taken along a redox gradient in alkaline, hypersaline Mono Lake, Calif. The form I gene (cbbL) was found in all samples, whereas form II (cbbM) was not retrieved from any of the samples. None of the RuBisCO sequences we obtained were closely related (nucleotide similarity, <90%) to sequences in the database. Some could be attributed to organisms isolated from the lake (Cyanobium) or appearing in enrichment cultures. Most (52%) of the sequences fell into in one clade, containing sequences that were identical to sequences retrieved from an enrichment culture grown with nitrate and sulfide, and another clade contained sequences identical to those retrieved from an arsenate-reducing, sulfide-oxidizing enrichment. 相似文献
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89.
Kurisu G Zakharov SD Zhalnina MV Bano S Eroukova VY Rokitskaya TI Antonenko YN Wiener MC Cramer WA 《Nature structural biology》2003,10(11):948-954
Cellular import of colicin E3 is initiated by the Escherichia coli outer membrane cobalamin transporter, BtuB. The 135-residue 100-A coiled-coil receptor-binding domain (R135) of colicin E3 forms a 1:1 complex with BtuB whose structure at a resolution of 2.75 A is reported. Binding of R135 to the BtuB extracellular surface (DeltaG(o) = -12 kcal mol(-1)) is mediated by 27 residues of R135 near the coiled-coil apex. Formation of the R135-BtuB complex results in unfolding of R135 N- and C-terminal ends, inferred to be important for unfolding of the colicin T-domain. Small conformational changes occur in the BtuB cork and barrel domains but are insufficient to form a translocation channel. The absence of a channel and the peripheral binding of R135 imply that BtuB serves to bind the colicin, and that the coiled-coil delivers the colicin to a neighboring outer membrane protein for translocation, thus forming a colicin translocon. The translocator was concluded to be OmpF from the occlusion of OmpF channels by colicin E3. 相似文献
90.
Anaerobic oxidation of arsenite in Mono Lake water and by a facultative,arsenite-oxidizing chemoautotroph,strain MLHE-1 总被引:1,自引:0,他引:1
Oremland RS Hoeft SE Santini JM Bano N Hollibaugh RA Hollibaugh JT 《Applied and environmental microbiology》2002,68(10):4795-4802
Arsenite [As(III)]-enriched anoxic bottom water from Mono Lake, California, produced arsenate [As(V)] during incubation with either nitrate or nitrite. No such oxidation occurred in killed controls or in live samples incubated without added nitrate or nitrite. A small amount of biological As(III) oxidation was observed in samples amended with Fe(III) chelated with nitrolotriacetic acid, although some chemical oxidation was also evident in killed controls. A pure culture, strain MLHE-1, that was capable of growth with As(III) as its electron donor and nitrate as its electron acceptor was isolated in a defined mineral salts medium. Cells were also able to grow in nitrate-mineral salts medium by using H(2) or sulfide as their electron donor in lieu of As(III). Arsenite-grown cells demonstrated dark (14)CO(2) fixation, and PCR was used to indicate the presence of a gene encoding ribulose-1,5-biphosphate carboxylase/oxygenase. Strain MLHE-1 is a facultative chemoautotroph, able to grow with these inorganic electron donors and nitrate as its electron acceptor, but heterotrophic growth on acetate was also observed under both aerobic and anaerobic (nitrate) conditions. Phylogenetic analysis of its 16S ribosomal DNA sequence placed strain MLHE-1 within the haloalkaliphilic Ectothiorhodospira of the gamma-PROTEOBACTERIA: Arsenite oxidation has never been reported for any members of this subgroup of the PROTEOBACTERIA: 相似文献