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71.
Akira Matsuda Krzysztof Pankiewicz Bonita K. Marcus Kyoichi.A. Watanabe Jack J. Fox 《Carbohydrate research》1982,100(1):297-302
The first chemical synthesis of 3-methyl-ψ-uridine (5) and its 2′-deoxy analogue (9) has been achieved. ψ-Uridine was trimethylsilylated and the crude product was treated with acetyl chloride, to give the 1-acetyl derivative (3). Crude 3 was methylated with dimethoxymethyldimethylamine and then saponified, to give crystalline 5 in 82% overall yield. Treatment of 5 with 1,3-dichloro-1,1,3,3-tetraiso-propyldisiloxane afforded the 3′,5′-protected product, which was converted into the 2′-O-[(imidazol-1-yl)thiocarbonyl] derivative 7. Reduction of 7 with tributyltin hydride followed by deblocking of the product gave crystalline 2′-deoxy-3-methyl-ψ-uridine (9) in 35% yield from 5. 相似文献
72.
Choi YY Osada K Ito Y Nagasawa T Choi MR Nishizawa N 《Bioscience, biotechnology, and biochemistry》2005,69(1):31-37
We examined the effects of intake of Korean foxtail millet protein (FMP) on plasma levels of lipid, glucose, insulin, and adiponectin in genetically type 2 diabetic KK-Ay mice. When mice were fed a normal FMP diet or a high-fat-high-sucrose diet containing FMP for 3 weeks, in both experiments plasma concentrations of high-density lipoprotein cholesterol (HDL-cholesterol) and adiponectin increased remarkably in comparison with a casein diet group, whereas concentrations of insulin decreased greatly and that of plasma glucose was comparable to that in the casein diet group. Considering the role of adiponectin, insulin, and HDL-cholesterol in diabetes, atherosclerosis, and obesity, it appears likely that FMP may improve insulin sensitivity and cholesterol metabolism through an increase in adiponectin concentration. Therefore, FMP would serve as another beneficial food component in obesity-related diseases such as type 2 diabetes and cardiovascular diseases. 相似文献
73.
The protein-bound polysaccharide isolated from basidiomycetes (PSK) is a biological response modifier capable of exhibiting various biological activities, such as antitumor and antimicrobial effects. In the present study, we found that PSK suppressed interleukin (IL)-6 production in murine peritoneal macrophages stimulated with endotoxic lipopolysaccharide (LPS) and its synthetic lipid A (compound 506). Nitric oxide production and p38 mitogen-associated protein kinase phosphorylation induced in a murine macrophage cell line, J774-A1, by LPS and compound 506 were also inhibited by PSK. Further, PSK distinctly suppressed nuclear factor-kappaB activation in Ba/F3 cells expressing mouse Toll-like receptor 4 and MD-2, following stimulation with LPS and compound 506, however, not with Taxol. These PSK-induced inhibitory activities were caused by inhibition of the physical associations of LPS with LPS-binding protein (LBP) and CD14. PSK also protected mice from LPS-induced lethality, presumably by down-regulating IL-6 and tumor necrosis factor-alpha concentrations in serum. These findings indicate that PSK, which also has an ability to regulate LBP/CD14 functions, may be useful for clinical control of endotoxic sepsis. 相似文献
74.
Synthesis and anti-HCV activity of N9,5'-cyclo-3-(beta-D-ribofuranosyl)-8-azapurin-2-one derivatives
Hassan AE Wang P McBrayer T Tharnish P Stuyver L Otto MJ Watanabe KA Schinazi RF 《Nucleosides, nucleotides & nucleic acids》2005,24(10-12):1531-1542
A number of 1- or 6-substituted N9,5'-cyclo-3-(beta-ribofuranosyl)-8-azapurin-2-one derivatives were synthesized in multi-step reactions. Their anti-hepatitis C virus activities were evaluated and some structure-activity relationship is discussed. 相似文献
75.
Role of nicotinamide adenine dinucleotide phosphate oxidase 1 in oxidative burst response to Toll-like receptor 5 signaling in large intestinal epithelial cells 总被引:12,自引:0,他引:12
Kawahara T Kuwano Y Teshima-Kondo S Takeya R Sumimoto H Kishi K Tsunawaki S Hirayama T Rokutan K 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(5):3051-3058
The NADPH oxidase 1 (Nox1) is a gp91(phox) homologue preferentially expressed in the colon. We have established primary cultures of guinea pig large intestinal epithelial cells giving 90% purity of surface mucous cells. These cells spontaneously released superoxide anion (O(2)(-)) of 160 nmol/mg protein/h and expressed the Nox1, p22(phox), p67(phox), and Rac1 mRNAs, but not the gp91(phox), Nox4, p47(phox), p40(phox), and Rac2 mRNAs. They also expressed novel homologues of p47(phox) and p67(phox) (p41(nox) and p51(nox), respectively). Human colon cancer cell lines (T84 and Caco2 cells) expressed the Nox1, p22(phox), p51(nox), and Rac1 mRNAs, but not the other NADPH component mRNAs, and secreted only small amounts of O(2)(-) (<2 nmol/mg protein/h). Cotransfection of p41(nox) and p51(nox) cDNAs in T84 cells enhanced PMA-stimulated O(2)(-) release 5-fold. Treatment of the transfected T84 cells with recombinant flagellin (rFliC) from Salmonella enteritidis further augmented the O(2)(-) release in association with the induction of Nox1 protein. The enhanced O(2)(-) production by cotransfection of p41(nox) and p51(nox) vectors further augmented the rFliC-stimulated IL-8 release from T84 cells. T84 cells expressed the Toll-like receptor 5, and rFliC rapidly phosphorylated TGF-beta-activated kinase 1 and TGF-beta-activated kinase 1-binding protein 1. A potent inhibitor for NF-kappaB (pyrrolidine dithiocarbamate) significantly blocked the rFliC-primed increase in O(2)(-) production and induction of Nox1 protein. These results suggest that p41(nox) and p51(nox) are involved in the Nox1 activation in surface mucous cells of the colon, and besides that, epithelial cells discern pathogenicities among bacteria to appropriately operate Nox1 for the host defense. 相似文献
76.
Yoshimi Ikemoto Satoru Ishizuka Kyoichi Ono Norio Akaike 《Cellular and molecular neurobiology》1988,8(3):293-305
1. Kinetics of activation and desensitization phases of the acetylcholine (ACh)-induced chloride current (ICI) were studied using isolated single neurons of Japanese land snail and the "concentration clamp" technique. 2. The dose-response curve for the peak ICI gave a dissociation constant of 7.1 x 10(-6) M and a Hill coefficient of 1.8. 3. The current-voltage relationship was linear in the voltage range examined (-60 to +10 mV) and the reversal potential (EACh) was -7.2 +/- 1.5 mV (N = 10). The value was close to the calculated equilibrium potential for chloride ions (ECI). 4. Both activation and desensitization phases of the ACh-induced ICI consisted of a single exponential at concentrations less than 3 x 10(-6) M and a double exponential at higher concentrations. The time constants of both phases decreased with increasing ACh concentrations but showed no potential dependency. 5. The recovery from desensitization of the ICI induced by 5 x 10(-6) M ACh proceeded double exponentially, with time constants of 11 and 114 sec at a holding potential of -30 mV. 6. Noise analysis was performed on a steady-state current induced by 3 x 10(-7) to 2 x 10(-6) M ACh. The mean open time was about 60 msec at 10(-6) M ACh and the single-channel conductance was 14 PS. 7. These results suggest that the ACh receptor-Cl channel complex in snail neurons has two binding sites with the dissociation constant of 7.1 x 10(-6) M and is rapidly activated and desensitized to a steady level in the presence of the agonist. 相似文献
77.
Ling-Ching Chen Tsann-Long Su Krzysztof W. Pankiewicz Kyoichi A. Watanabe 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1179-1188
Abstract In an attempt to introduce a substituent at C-2′ in the “up” arabino configuration directly by nucleophilic displacement reaction of a preformed pyrimidine ribonucleoside, we synthesized 2,5′-anhydro-5′-deoxy-2-thiouridine (6) in three steps from uridine. Compound 6 was converted into the 3′-O-acetyl derivative 7. Upon treatment of 7 with triflyl chloride in methylene chloride in the presence of triethylamine and p-dimethylaminopyridine, 2,2′-anhydro-1-(3-O-acetyl-5-chloro-2,5-dideoxy-β-D-arabinofuranosyl)-2-thiouracil (9) was obtained as the only isolable product. Obviously, the intermediate 3′-O-acetyl-2,5′-anhydro-2′-O-triflyl-2-thiouridine (8) was attacked by the chloride nucleophile at C-5′ first giving the 2′-O-triflyl-2-thiouridine intermediate from which 9 was formed by intramolecular nucleopilic reaction. 相似文献
78.
Natalia Dyatkina Alexander Khorlin Kyoichi A. Watanabe 《Nucleosides, nucleotides & nucleic acids》2013,32(3):585-591
Abstract Thymine and 2′,3′,5′-tri-O-acetyl-Ψ-uridine (1) was converted into the corresponding 2,4-ditriazolyl derivatives 5 and 2, respectively. Of these two substituents, the C4-triazolyl group was found to be quite susceptible to nucleophilic substitution while the other triazolyl is resistant. 相似文献
79.
The evolutionary design of genetic switches and circuits requires iterative rounds of positive (ON-) and negative (OFF-) selection. We previously reported a rapid OFF selection system based on the kinase activity of herpes simplex virus thymidine kinase (hsvTK) on the artificial mutator nucleoside dP. By fusing hsvTK with the kanamycin resistance marker aminoglycoside-(3’)-phosphotransferase (APH), we established a novel selector system for genetic switches. Due to the bactericidal nature of kanamycin and nucleoside-based lethal mutagenesis, both positive and negative selection could be completed within several hours. Using this new selector system, we isolated a series of homoserine lactone-inducible genetic switches with different expression efficiencies from libraries of the Vibrio fischeri lux promoter in two days, using only liquid handling. 相似文献
80.
The first committed steps of steroid/hopanoid pathways involve squalene synthase (SQS). Here, we report the Escherichia coli production of diaponeurosporene and diapolycopene, yellow C30 carotenoid pigments, by expressing human SQS and Staphylococcus aureus dehydrosqualene (C30 carotenoid) desaturase (CrtN). We suggest that the carotenoid pigments are synthesized mainly via the desaturation of squalene rather than the direct synthesis of dehydrosqualene through the non-reductive condensation of prenyl diphosphate precursors, indicating the possible existence of a “squalene route” and a “lycopersene route” for C30 and C40 carotenoids, respectively. Additionally, this finding yields a new method of colorimetric screening for the cellular activity of squalene synthases, which are major targets for cholesterol-lowering drugs. 相似文献