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51.
A Pd(II) complex containing didentate triazine ligand L1 (2-(2-methylphenyl)-3-(2-pyridyl)-2,3-dihydronaphtho[2,1-e][1,2,4]triazine) [PdCl2(L1)] (1) was prepared, and the structure was determined by X-ray crystallography. The absorption spectrum of complex 1 in dichloromethane changed gradually with isosbestic points when methanol was added to the solution, and [PdCl(L2)] (2) (L2 = N-[methoxy(2-pyridyl)methyl]-1-(2-methylphenylazo)-2-naphthylamide) was obtained from the resulting solution after the reaction was completed. Addition of hydrogen chloride to the solution of complex 2 led to the recovery of complex 1. Thus, a reversible ring opening and closure reaction of the triazine ligand was observed. The progress of the ring opening reaction was monitored by observing the absorbance changes at several wavelengths of the visible spectra as a function of the concentration of methanol. The absorbance plots were fitted successfully with a mechanism that includes the consumption of two methanol molecules and the release of HCl, whose concentration is equivalent to that of the produced Pd complex . In dichloromethane with a low dielectric constant, the polar HCl molecule will be stabilized by forming an adduct with methanol. The equilibrium constant was determined as at T = 25.0 °C. The kinetics of the reaction of [PdCl2(L1)] with methanol was investigated by monitoring the absorbance change of the reacting solution with time. We obtained rate constant values of k1 = (2.40 ± 0.07) × 10−3 s−1 and k2 = (5.8 ± 0.1) × 10−3 M−1 s−1 at T = 25.0 °C on the observed pseudo-first-order rate constant of the forward reaction, kf = k1 + k2 [CH3OH]. 相似文献
52.
Ohtake Y Sato T Matsuoka H Nishimoto M Taka N Takano K Yamamoto K Ohmori M Higuchi T Murakata M Kobayashi T Morikawa K Shimma N Suzuki M Hagita H Ozawa K Yamaguchi K Kato M Ikeda S 《Bioorganic & medicinal chemistry》2011,19(18):5334-5341
5a-Carba-β-D-glucopyranose derivatives were synthesized and identified as novel SGLT2-selective inhibitors. These inhibitors exhibited potent SGLT2 inhibition with high selectivity over SGLT1. Among the tested compounds, 6f indicated the most potent hSGLT2 inhibition and the highest selectivity over hSGLT1. Moreover, the pharmacokinetics data also showed that 6h, which had the same aglycon structure as sergliflozin-active (3-active), had a threefold longer half-life time (T(1/2)) than sergliflozin (3) with a high distribution volume in db/db mice. Subsequently, 6h lowered blood glucose levels as much as 3 and showed longer hypoglycemic action than 3 in db/db mice. 相似文献
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Jun Qian Shinji Ito Junko Satoh Hongmin Geng Keisuke Tanaka Shunji Hattori 《Bioscience, biotechnology, and biochemistry》2017,81(3):514-522
Bovine type I collagen consists of two α1 and one α2 chains, containing the internal triple helical regions and the N- and C-terminal telopeptides. In industries, it is frequently digested with porcine pepsin to produce a triple helical collagen without the telopeptides. However, the digestion mechanism is not precisely understood. Here, we performed a mass spectrometric analysis of the pepsin digest of the N-terminal telopeptide pQLSYGYDEKSTGISVP (1–16) in the α1 chain. When purified collagen was digested, pQLSYGY (1–6) and pQLSYGYDEKSTG (1–12) were identified, while DEKSTG (7–12) was not. When the N-terminal telopeptide mimetic synthetic peptide pQLSK(MOCAc)GYDEKSTGISK(Dnp)P-NH2 was digested, pQLSK(MOCAc)GYDEKSTG (1–12) and ISK(Dnp)P-NH2 (13?16) were readily identified, pQLSK(MOCAc)GY (1?6) and DEKSTGISK(Dnp)P-NH2 (7?16) were weakly detected, and DEKSTG (7–12) was hardly identified. These results suggest that pepsin preferentially cleaves Tyr6–Asp7 and less preferentially Gly12–Ile13. They also suggest that the former cleavage requires native collagen structure, while the latter cleavage does not. 相似文献
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Bani Mukhopadhyay Jie Liu Douglas Osei-Hyiaman Grzegorz Godlewski Partha Mukhopadhyay Lei Wang Won-Il Jeong Bin Gao Gregg Duester Ken Mackie Soichi Kojima George Kunos 《The Journal of biological chemistry》2010,285(25):19002-19011
Alcoholism can result in fatty liver that can progress to steatohepatitis, cirrhosis, and liver cancer. Mice fed alcohol develop fatty liver through endocannabinoid activation of hepatic CB1 cannabinoid receptors (CB1R), which increases lipogenesis and decreases fatty acid oxidation. Chronic alcohol feeding also up-regulates CB1R in hepatocytes in vivo, which could be replicated in vitro by co-culturing control hepatocytes with hepatic stellate cells (HSC) isolated from ethanol-fed mice, implicating HSC-derived mediator(s) in the regulation of hepatic CB1R (Jeong, W. I., Osei-Hyiaman, D., Park, O., Liu, J., Bátkai, S., Mukhopadhyay, P., Horiguchi, N., Harvey-White, J., Marsicano, G., Lutz, B., Gao, B., and Kunos, G. (2008) Cell Metab. 7, 227–235). HSC being a rich source of retinoic acid (RA), we tested whether RA and its receptors may regulate CB1R expression in cultured mouse hepatocytes. Incubation of hepatocytes with RA or RA receptor (RAR) agonists increased CB1R mRNA and protein, the most efficacious being the RARγ agonist CD437 and the pan-RAR agonist TTNPB. The endocannabinoid 2-arachidonoylglycerol (2-AG) also increased hepatic CB1R expression, which was mediated indirectly via RA, because it was absent in hepatocytes from mice lacking retinaldehyde dehydrogenase 1, the enzyme catalyzing the generation of RA from retinaldehyde. The binding of RARγ to the CB1R gene 5′ upstream domain in hepatocytes treated with RAR agonists or 2-AG was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift and antibody supershift assays. Finally, TTNPB-induced CB1R expression was attenuated by small interfering RNA knockdown of RARγ in hepatocytes. We conclude that RARγ regulates CB1R expression and is thus involved in the control of hepatic fat metabolism by endocannabinoids. 相似文献
56.
Matsuda K Miura T Kaiya H Maruyama K Shimakura S Uchiyama M Kangawa K Shioda S 《Peptides》2006,27(9):2321-2325
Our recent research has indicated that intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of n-octanoic acid-modified ghrelin (acyl ghrelin) stimulates food intake and locomotor activity in the goldfish. The manner in which peripherally administered acyl ghrelin regulates food intake, however, remains unclear. In contrast to acyl ghrelin, non-acylated ghrelin (des-acyl ghrelin) does not exert an orexigenic action or induce hypermotility. To this extent, the biological role of des-acyl ghrelin in fish is unknown. Given the possible involvement of afferent pathways in mediating the effects of acyl ghrelin, as is known to occur in rodents, we examined the effect of capsaicin, a neurotoxin which destroys primary sensory (vagal and splanchnic) afferents, on the orexigenic activity induced by i.p.-injected acyl ghrelin. Pretreatment with i.p.-injected capsaicin (0.16 micromol/g body weight (BW)) cancelled the orexigenic action of i.p.-injected acyl ghrelin (8 pmol/g BW), although i.p.-injected capsaicin alone did not affect food intake. The effect of des-acyl ghrelin on the orexigenic action of acyl ghrelin in the goldfish was also investigated. The i.c.v. and i.p. injection of des-acyl ghrelin at doses 3-10 times higher than that of acyl ghrelin suppressed the orexigenic action of i.c.v.- and i.p.-injected acyl ghrelin (doses of 1 and 8 pmol/g BW). In contrast, injection of des-acyl ghrelin alone did not show any inhibitory effect on food intake. These results suggest that, as is seen in rodents, circulating acyl ghrelin derived from peripheral tissues acts via primary sensory afferent pathways on feeding centers in the brain. The results also show that des-acyl ghrelin inhibits acyl ghrelin-induced orexigenic activity in goldfish. 相似文献
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Association constants and maximum binding numbers of sulfatide- and phosphatidylserine (PS)-containing liposomes for their binding with adriamycin (ADM) were determined by the column equilibration method. Although these liposomes have two kinds of binding sites, hydrophobic and electrostatic, the majority of ADM molecules was associated with the liposomes via their latter binding sites. Since the association constant for the electrostatic binding of ADM was smaller in sulfatide-containing liposomes (3 x 10(3) M-1) than in PS-containing ones (1.1 x 10(4) M-1), high efficiency of sulfatide-containing liposomes for the entrapment of ADM might be explained by the effect of sulfatide making the liposomes rigid, thereby preventing the leakage of the entrapped ADM. 相似文献
60.