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排序方式: 共有286条查询结果,搜索用时 281 毫秒
91.
Nicholas M. Kelly Anja Wellejus Heidi Elbrønd-Bek Morten Sloth Weidner Signe Humle Jørgensen 《Bioorganic & medicinal chemistry》2013,21(11):3334-3347
Esaprazole, a molecule previously acknowledged to protect against stomach and intestinal ulcers was surprisingly discovered to have neuroprotective activities and σ1 binding in vitro. A highly diverse set of Esaprazole analogues 2–5 was prepared in order to increase blood–brain barrier penetration. The analogues showed a structure–activity relationship at the σ1 receptor closely matching already published pharmacophores. Many of the analogues were shown to have neuroprotective properties in two assays using primary cultures of cortical neurons exposed to glutamate and hydrogen peroxide. However, no apparent SAR for these two assays could be developed. Metabolic stability of the analogues were also investigated and the structure of R1 had a significant bearing on the ADME properties of the compound resulting in two series of compounds. Compounds in which R1 was a H or acyl group had good metabolic stability in RLM but poor BBB penetration, whereas compounds where R1 was a cyclo- or bicyclo-alkyl group had poor metabolic stability but good BBB penetration. 相似文献
92.
93.
The growth rate of Laminaria saccharina (L.) Lamour. is dependent on inorganic nitrogen in culture. Growth rates were saturated between 5 and 10 μmol · L?1 nitrate. The activities of ribulose-1,5 bisphosphate carboxylase, phosphoenolpyruvate carboxykinase, mannitol-1-phosphate dehydrogenase, nitrate reductase and glutamine synthetase also varied with the concentration of inorganic nitrogen in the medium. All enzyme activities were lowest at 2.5 μmol · L?1 nitrate (the lowest concentration used) increasing to a maximum activity between 10 and 30 μmol · L?1 nitrate. Most enzyme activities followed a hyperbolic curve resembling those described by the Michaelis-Menten equation, with different half-saturation constants. 相似文献
94.
High affinity murine anti-fluorescein monoclonal antibody (Mab) 4-4-20 (K alpha = 1.3 x 10(10) M-1; IgG2a; kappa), affinity labeled with fluorescein isothiocyanate (I), served as the immunogen to elicit a xenogenic (rabbit) polyclonal "anti-metatype" reagent in a rabbit specific for the liganded state. The reagent did not bind Mab 4-4-20 in its nonliganded (idiotypic) conformation and demonstrated no reactivity with fluorescein ligand. Interaction of the anti-metatype reagent with liganded 4-4-20 caused a significant decrease in the dissociation rate of fluorescyl ligand bound to Mab 4-4-20 and a single-chain antibody derivative of 4-4-20. Additionally, most members of the 4-4-20 idiotype family displayed the same kinetic effect in the presence of anti-metatype. Members most closely related to Mab 4-4-20 (based on concentration in Mab required to inhibit the 4-4-20 idiotype/4-4-20 anti-idiotype interaction 50%) showed relatively greater decreases in the dissociation rate, establishing a quantitative correlation between idiotype and metatype. The immunologically distinct metatypic state is discussed in terms of conformational changes in or near the active site upon binding ligand, possibly involving two amino acid residues which "close off" the mouth of the antibody-active site upon binding fluorescein. 相似文献
95.
The patterns of seasonal variation of enzyme levels in the brown alga Laminaria hyperborea (Gunn.) Fosl. have been investigated for the following enzymes: Ribulosebisphosphate-carboxylase (EC 4.1.1.39), phosphoenolpyruvate-carboxykinase (EC 4.1.1.32), glyceraldehyde-3-phosphate-dehydrogenase (NADP dep., EC 1.2.1.12), malate-dehydrogenase (NAD dep., EC 1.1.1.37), L-aspartate-2-oxoglutarate aminotransferase (EC 2.6.1.1), and mannitol-l-phosphate-dehydrogenase (EC 1.1.1.17). The first four enzymes exhibit a circannual periodicity, characterized by a pronounced spring-maximum of enzyme activity in April and May. As a consequence, the phylloid can maintain high metabolic rates from early spring on, although water temperature has then only slightly risen above the annual minimum. This findings is discussed in relationship to the growth- and developmental cycle of L. hyperborea and to the seasonal variation of photosynthesis and light-independent CO2-fixation. The seasonal pattern, outlined above, correlates well with the circannual fluctuations of the nitrogen content of the sea and with the variation of the internal nitrogen- and nitrate-content of the alga. This coincidence may indicate that nitrogen levels play an important role in the regulation of enzyme activities and, hence, the metabolic capacities of L. hyperborea.Abbreviations PEPCK
phosphoenolpyruvate carboxykinase (EC 4.1.1.32)
- RUBPC
ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39)
- GAPDH (NADP dep.)
glyceraldehyde-3-phosphate dehydrogenase (NADP dependent) (EC 1.2.1.12)
- MDH (NAD dep.)
malate dehydrogenase (NAD dependent) (EC 1.1.1.37)
- AAT
L-aspartate-2-oxoglutarate aminotransferase (EC 2.6.1.1)
- Mannitol-1-P DH
mannitol-1-phosphate dehydrogenase (EC 1.1.1.17)
- LIF
lightindependent CO2-fixation
- DHAP
dihydroacetone phosphate
- PEP
phosphoenolpyruvate
- 3-PGA
3-phosphoglycerate
- OAA
oxaloacetate 相似文献
96.
The nucleotide sequence preferences of the DNA interstrand cross-linking agents dehydroretronecine diacetate (DHRA), 2,3-bis(acetoxymethyl)-1-methylpyrrole (BAMP), dehydromonocrotaline, and dehydroretrorsine were studied by using synthetic DNA duplex fragments and polyacrylamide gel electrophoresis (PAGE). These agents have structural features in common with the reductively activated aziridinomitosene of mitomycin C (MC). Like MC, they preferentially cross-linked DNA duplexes containing the duplex sequence 5'-CG. For DHRA and BAMP interstrand cross-linked DNA duplexes, PAGE analysis of iron(II)-EDTA fragmentation reactions revealed the interstrand cross-links to be deoxyguanosine to deoxyguanosine (dG-to-dG), again analogous to DNA cross-links caused by MC. Unlike MC, DHRA could be shown to dG-to-dG cross-link a 5'-GC sequence. Furthermore, the impact of flanking sequence on the efficiency of interstrand cross-linking at 5'-CG was reduced for BAMP, with 5'-TCGA and 5'-GCGC being equally efficiently cross-linked. Possible origins of the 5'-CG sequence recognition common to all of the agents are discussed. A model is presented in which the transition state for the conversion of monoadducts to cross-links more closely resembles ground-state DNA at 5'-CG sequences. 相似文献
97.
The optimum temperature of protein synthesis in wheat seedlings (Triticum aestivum L.), measured as 14C-leucine incorporation, depends on the growing temperature. Plants grown at reduced temperature (4 C) reach their optimum at 27.5 C, whereas plants kept at 36 C have the highest rate of protein synthesis at 35 C. The transition is gradual. The activation energy of protein synthesis for seedlings grown at medium or reduced temperature is lower (about 11 kcal/mole), than for plants grown at higher temperatures (15 keal/mole). The decline of the rate of protein synthesis beyond the temperature optimum is also affected by the growth temperature; only plants kept at 30 or 36 C show a sharp decrease with increasing slope; plants kept at 4, 10, and 20 C exhibit a linear and comparatively moderate decline. 相似文献
98.
Interactions between Encephalitozoon cuniculi and macrophages. Parasitophorous vacuole growth and the absence of lysosomal fusion. 总被引:12,自引:0,他引:12
E Weidner 《Zeitschrift für Parasitenkunde (Berlin, Germany)》1975,47(1):1-9
Encephalitozoon cuniculi grow within ever-increasing parasitophorous vacuoles (PV) in peritoneal macrophages. The PV boundary membrane conforms to a rich arrangement of blebs; similar, but free vesicles were observed within the PV space. An iron dextran-concanavalin A marker was used to express visually clustered distributions of Con A receptors on the PV boundary blebs and free vesicles; no marker was observed on other membrane surfaces within the PV. These results, combined with the observation that the PV grows while the host cytoplasm decreases in mass, implicate the PV boundary blebs of interiorizing into vesicles by a pinocytic mechanism. Phagocytic vacuoles, secondary lysosomes and pinocytic vesicles were labeled by incubating infected macrophages in minimum essential medium with ferritin. Ferritin readily accumulated in secondary lysosomes and phagocytic vacuoles; however, ferritin was excluded from parasitophorous vacuoles containing E. cuniculi. Acid phosphatase cytochemical reaction product was observed in lysosomes and phagocytic vacuoles; however, parasitophorous vacuoles with vegetative E. cuniculi were always negative. 相似文献
99.
The effect of low-, ambient- and high-temperature pretreatments (48 h at 4° C, 20° C or 36° C) of wheat seedlings (spring wheat Triticum aestivum L., cv. Kolibri) on the solubility properties of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPCase; EC 4.1.1.39) was studied. The extractable protein moiety of heat-pretreated plants exhibited increased solubility in dilute buffer (50 mM k-phosphate, pH 6.8), compared with protein extracted from 4° C- or 20° C-plants. The salting-out characteristics for ammonium-sulfate precipitation confirmed this finding since a delayed precipitation of extractable protein from 36°C-plants was observed. Using polyacrylamide gel electrophoresis, the in-vivo temperature-induced differences in protein solubility could be traced back to a change in the solubility of RuBPCase. The RuBPCase was purified from wheat seedlings, and the purified enzyme also exhibited differential solubility. In order to evaluate this further, purified RuBPCase was subjected to probing for conformational properties. A decrease of fluorescence of the RuBPCase 1-anilino-8-naphtalene sulfonate complex revealed that the RuBPCase from 36° C-plants had a more hydrophilic protein surface. Titration of the sulfhydryl groups of native RuBP-Case with 5,5-dithiobis (2-nitrobenzoic acid) pointed to a reduced accessibility of the R-SH groups in the case of the 36° C-type of RuBPCase. The large subunit of RuBPCase from 4° C/20° C-plants tended to give rise to an artificial lower-molecular-weight polypeptide which could not be found in crude or purified RuBPCase from heat-pretreated wheat seedlings.Abbreviations ANS
1-anilino-8-naphtalene sulfonate
- DTNB
5,5-dithiobis(2-nitrobenzoic acid)
- PAGE
polyacrylamide gel electrophoresis
- RuBPCase
ribulose-1,5-bis-phosphate carboxylase/oxygenase
- RuBP
ribulose-1,5-bis-phosphate 相似文献
100.
Phagocytized intracellular microsporidian blocks phagosome acidification and phagosome-lysosome fusion 总被引:4,自引:0,他引:4
This study examines the relationship between phagosome acidification and phagosome-lysosome fusion events using phagocytized Glugea hertwigi spores. The incidence of lysosome fusion with Glugea spores in phagosomes of mouse peritoneal macrophages and of Tetrahymena was monitored using colloidal gold and acridine orange as labels for secondary lysosomes. Over 80% of the Glugea phagosomes remained segregated from the labeled compartments in macrophages after 60 min; this inhibition of fusion was still evident after 4 h. In Tetrahymena, Glugea spores also showed a high capacity to block fusion with secondary lysosomes (67%); however, spores coated with cationized ferritin showed an 80% fusion rate with labeled acidic compartments (i.e. lysosomes) after 60 min with both Tetrahymena and macrophages. The pH of phagosome compartments was monitored by measuring the emissions of fluorescein isothiocyanate (FITC)-labeled Glugea ingested by Tetrahymena. Tetrahymena phagosomes with FITC-Glugea did not acidify within the first hour after phagocytosis; however, phagosomes with cationized ferritin-labeled Glugea underwent acidification during this time period. This acidification took place although the capability of the host cells' lysosomes to fuse was blocked by pretreatment with poly-D-glutamic acid. The cationized ferritin bound to Glugea spores was uncoupled from the spore wall prior to fusion with colloidal gold-labeled compartments. In vitro testing showed that ferritin dissociation requires an acid pH, indicating that phagosomes acidify prior to lysosome fusion. 相似文献