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排序方式: 共有440条查询结果,搜索用时 15 毫秒
31.
Yukio Miyazaki Mitsuaki Mitani Noboru Ōtake 《Bioscience, biotechnology, and biochemistry》2013,77(11):2133-2138
SY-1 (20-deoxysalinomycin), a monocarboxylic polyether antibiotic closely related to salinomycin, caused a rapid release of previously accumulated alkali metal cations by valinomycin or monazomycin in rat liver mitochondria, and simultaneously reversed swelling of mitochondria.With a strict specificity for substrate and cation, SY-1 exhibited a property of inhibiting mitochondrial functions such as substrate oxidation, oxidative phosphorylation and ATP hydrolysis induced by valinomycin or monazomycin, In comparative study with salinomycin, SY-1 was found to be more effective on the mitochondrial functions than salinomycin.On the basis of the results so far obtained, the inhibitory effect of SY-1 on mitochondria is interpreted as a result of interaction with essential cations, especially with K+, in mitochondria. 相似文献
32.
The potential use of alpha-cyclodextrin and its hydrophilic alpha-cyclodextrin derivatives (alpha-CyDs) as antagonists against lipopolysaccharide (LPS), which stimulates the nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production as well as nuclear factor-kappaB (NF-kappaB) activation in macrophages was examined. Of three alpha-CyDs used in the present study, 2,6-di-O-methyl-alpha-CyD (DM-alpha-CyD) had greater inhibitory activity than did the other CyDs against NO and TNF-alpha production through an impairment of gene expression in macrophage cell lines and primary macrophages stimulated with LPS and lipid A in a concentration-dependent manner. Concomitantly, DM-alpha-CyD inhibited NF-kappaB translocation into nucleus. These inhibitory effects of DM-alpha-CyD could be attributed to the release of CD14 from lipid rafts caused by an efflux of phospholipids, but not cholesterol. These results suggest that DM-alpha-CyD may have promise as a potent and unique antagonist for excess activation of macrophages stimulated with LPS. 相似文献
33.
Keith L. Constantine Mark S. Friedrichs David Detlefsen Maki Nishio Mitsuaki Tsunakawa Tamotsu Furumai Hiroaki Ohkuma Toshikazu Oki Susan Hill Robert E. Bruccoleri Pin-Fang Lin Luciano Mueller 《Journal of biomolecular NMR》1995,5(3):271-286
Summary The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell culture. The primary sequence of siamycin II is CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid; it has a valine residue at position 4. In both peptides, disulfide bonds link Cys1 with Cys13 and Cys7 with Cys19, and the side chain of Asp9 forms an amide bond with the N-terminus. Siamycin II, when dissolved in a 50:50 mixture of DMSO and H2O, yields NOESY spectra with exceptional numbers of cross peaks for a peptide of this size. We have used 335 NOE distance constraints and 13 dihedral angle constraints to generate an ensemble of 30 siamycin II structures; these have average backbone atom and all heavy atom rmsd values to the mean coordinates of 0.24 and 0.52 Å, respectively. The peptide displays an unusual wedge-shaped structure, with one face being predominantly hydrophobic and the other being predominantly hydrophilic. Chemical shift and NOE data show that the siamycin I structure is essentially identical to siamycin II. These peptides may act by preventing oligomerization of the HIV transmembrane glycoprotein gp41, or by interfering with interactions between gp41 and the envelope glycoprotein gp120, the cell membrane or membrane-bound proteins [Frèchet, D. et al. (1994) Biochemistry, 33, 42–50]. The amphipathic nature of siamycin II and siamycin I suggests that a polar (or apolar) site on the target protein may be masked by the apolar (or polar) face of the peptide upon peptide/protein complexation.Abbreviations ABNR
adopted basis Newton Raphson
- AIDS
acquired immunodeficiency syndrome
- CW
continuous wave
- DMSO
dimethylsulfoxide
- DQF-COSY
two-dimensional double-quantum-filtered correlation spectroscopy
- HIV
human immunodeficiency virus
- HSQC
heteronuclear single-quantum coherence
- NOE
nuclear Overhauser enhancement
- NOESY
two-dimensional nuclear Overhauser enhancement spectroscopy
- ppm
parts per million
- P.E.-COSY
two-dimensional primitive exclusive correlation spectroscopy
- REDAC
redundant dihedral angle constraint
- rf
radio frequency
- rmsd
root-mean-square difference
- SIV
simian immunodeficiency virus
- sw
spectral width
- m
mixing time
- TOCSY
two-dimensional total correlation spectroscopy
- TSP
trimethylsilyl-2,2,3,3-2H4-propionate
- 2D
two-dimensional 相似文献
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35.
Polypseudorotaxanes of pegylated insulin with cyclodextrins: application to sustained release system
Higashi T Hirayama F Arima H Uekama K 《Bioorganic & medicinal chemistry letters》2007,17(7):1871-1874
The monosubstituted insulin with poly(ethylene glycol) (PEG, MW about 2200) formed polypseudorotaxanes with alpha- and gamma-cyclodextrins (CyDs), by inserting one PEG chain of the pegylated insulin in the alpha-CyD cavity and two PEG chains in the gamma-CyD cavity. The pegylated insulin/alpha- and gamma-CyD polypseudorotaxanes were less soluble in water and the release rate of the drug decreased in the order of drug alone > the gamma-CyD polypseudorotaxane > the alpha-CyD polypseudorotaxane. The subcutaneous administration of the pegylated insulin/gamma-CyD polypseudorotaxane in rats significantly sustained plasma glucose levels with an enhanced hypoglycemic effect. The results indicated that the pegylated insulin/CyD polypseudorotaxanes can work as a sustained drug release system and the polypseudorotaxane formation may be useful as a sustained drug delivery technique for pegylated proteins and peptides. 相似文献
36.
37.
Diversity of Helicobacter pylori cagA and vacA genes in Costa Rica: its relationship with atrophic gastritis and gastric cancer 总被引:3,自引:0,他引:3
Con SA Takeuchi H Valerín AL Con-Wong R Con-Chin GR Con-Chin VG Nishioka M Mena F Brenes F Yasuda N Araki K Sugiura T 《Helicobacter》2007,12(5):547-552
BACKGROUND: Associations between Helicobacter pylori gene diversity and gastric cancer have not been reported on in Costa Rica, despite its being one of the countries with the highest gastric cancer incidence and mortality rates in the world. The aim of this study was to determine the prevalence of H. pylori cagA and vacA genes and investigate whether it could be correlated with atrophic gastritis (AG) and gastric cancer (GC) in Costa Rica. MATERIALS AND METHODS: Genomic DNAs from isolates of 104 patients classified into two groups: non-atrophic gastritis group (n = 68) and atrophic gastritis group (n = 36), were subjected to PCR-based genotyping of cagA and vacA genes and their correlation with clinical outcome was investigated. Total DNA extractions from gastric tissues of 25 H. pylori-infected gastric cancer patients were utilized for comparative purposes. RESULTS: The presence of cagA (75.3%), vacA s1b (75.3%), and vacA m1 (74.2%) was detected, and colonization by strains with different vacA genotypes in the same stomach was found in 9.7% of the patients. Age- and sex-adjusted vacA s1b and vacA m1 were associated with GC while only vacA m1 was significantly associated with AG. A tendency for association between cagA and vacA s1b, and AG was reported. CONCLUSIONS: The prevalence status of the cagA and vacA (s1/m1) genes in Costa Rica seems to fall between that found in European/North American and East Asian countries, and both cagA and vacA seem to have clinical relevance in this country. 相似文献
38.
Yano S Haruta H Ikeda T Kikuchi T Murakami M Moriguchi M Wakayama M 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(29):3247-3252
D-Aminoacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6 (AxD-NAase) offers a novel biotechnological application, the production of D-amino acid from the racemic mixture of N-acyl-DL-amino acids. However, its substrate specificity is biased toward certain N-acyl-D-amino acids. To construct mutant AxD-NAases with substrate specificities different from those of wild-type enzyme, the substrate recognition site of the AxD-NAase was rationally manipulated based on computational structural analysis and comparison of its primary structure with other D-aminoacylases with distinct substrate specificities. Mutations of amino acid residues, Phe191, Leu298, Tyr344, and Met346, which interact with the side chain of the substrate, induced marked changes in activities toward each substrate. For example, the catalytic efficiency (k(cat)/K(m)) of mutant F191W toward N-acetyl-D-Trp and N-acetyl-D-Ala was enhanced by 15.6- and 1.5-folds, respectively, compared with that of the wild-type enzyme, and the catalytic efficiency (k(cat)/K(m)) of mutant L298A toward N-acetyl-D-Trp was enhanced by 4.4-folds compared with that of the wild-type enzyme. Other enzymatic properties of both mutants, such as pH and temperature dependence, were the same as those of the wild-type enzyme. The F191W mutant in particular is considered to be useful for the enzymatic production of D-Trp which is an important building block of some therapeutic drugs. 相似文献
39.
Kubo A Stull R Takeuchi M Bonham K Gouon-Evans V Sho M Iwano M Saito Y Keller G Snodgrass R 《PloS one》2011,6(9):e24058
In order to define the molecular mechanisms regulating the specification and differentiation of pancreatic β-islet cells, we investigated the effect of upregulating Pdx1 and Ngn3 during the differentiation of the β-islet-like cells from murine embryonic stem (ES) cell-derived activin induced-endoderm. Induced overexpression of Pdx1 resulted in a significant upregulation of insulin (Ins1 and Ins2), and other pancreas-related genes. To enhance the developmental progression from the pancreatic bud to the formation of the endocrine lineages, we induced the overexpression express of Ngn3 together with Pdx1. This combination dramatically increased the level and timing of maximal Ins1 mRNA expression to approximately 100% of that found in the βTC6 insulinoma cell line. Insulin protein and C-peptide expression was confirmed by immunohistochemistry staining. These inductive effects were restricted to c-kit(+) endoderm enriched EB-derived populations suggesting that Pdx1/Ngn3 functions after the specification of pancreatic endoderm. Although insulin secretion was stimulated by various insulin secretagogues, these cells had only limited glucose response. Microarray analysis was used to evaluate the expression of a broad spectrum of pancreatic endocrine cell-related genes as well as genes associated with glucose responses. Taken together, these findings demonstrate the utility of manipulating Pdx1 and Ngn3 expression in a stage-specific manner as an important new strategy for the efficient generation of functionally immature insulin-producing β-islet cells from ES cells. 相似文献
40.