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Dong M Si YQ Sun SY Pu XP Yang ZJ Zhang LR Zhang LH Leung FP Lam CM Kwong AK Yue J Zhou Y Kriksunov IA Hao Q Lee HC 《Organic & biomolecular chemistry》2011,9(9):3246-3257
Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca(2+) messenger molecule, cyclic ADP-ribose, from NAD(+). It is well established that this novel Ca(2+) signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD(+) complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound 1-14). A number of these compounds exhibited moderate inhibition of the NAD(+) utilizing activity of CD38, with Compound 4 showing the highest potency. The crystal structure of CD38/Compound 4 complex and computer simulation of Compound 7 docking to CD38 show a significant role of the nicotinamide moiety and the distal aromatic group of the compounds for substrate recognition by the active site of CD38. Biologically, we showed that both Compounds 4 and 7 effectively relaxed the agonist-induced contraction of muscle preparations from rats and guinea pigs. This study is a rational design of inhibitors for CD38 that exhibit important physiological effects, and can serve as a model for future drug development. 相似文献
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Absorption and emission spectra at room temperature and emission spectra atliquid nitrogen temperature are reported for thin solid films of free base octaethylporphin. The room temperature visible absorption spectrum resembles that of the solution, except all four peaks show a red shift of ≈ 12 nm and all except the farthest red are broadened. The Soret band in the near UV is greatly broadened in the film, and its peak absorbance is substantially reduced. The room-temperature emission of the films is quite similar to that of solution fluorescence, except for a red-shift of ≈ 10 nm. But at low temperature two new peaks appear at 657 and 672 nm. Their intensity as a function of temperature can be explained by a simple exciton trapping model. 相似文献
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VCSEL Injection locking is demonstrated to increase laser bandwidth and reduce non-linearity and chirp.All these properties enhance analog and digital modulation performance. 相似文献
15.
Lee CK Holmes AB Ley SV McConvey IF Al-Duri B Leeke GA Santos RC Seville JP 《Chemical communications (Cambridge, England)》2005,(16):2175-2177
Suzuki cross-coupling reactions are effected in both conventional organic solvents, under continuous flow conditions at 70 degree C, and in batch mode in supercritical carbon dioxide (scCO2), at temperatures as low as 40 degrees C in the presence of palladium(II) acetate microencapsulated in polyurea [PdEnCat] and tetra-n-butylammonium salts. 相似文献
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Above,below, and in‐between the two glass transitions of ultrathin free‐standing polystyrene films: Thermal expansion coefficient and physical aging
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In previous work we observed two simultaneous transitions in high molecular weight (MW) free‐standing polystyrene films that were interpreted as two thickness‐dependent reduced glass transition temperatures (Tgs). The weaker lower transition agreed well with the MW‐dependent Tg(h) previously reported, while the much stronger upper transition matched the MW‐independent Tg(h) previously observed in low‐MW free‐standing films. Here, we investigate the nature of these two transitions by inspecting the temperature dependence of the films' thermal coefficient of expansion (TCE) and present physical aging measurements using ellipsometry both below and in‐between the two transitions. TCE values indicate approximately 80 to 90% of the film solidifies at the upper transition, while only 10 to 20% remains mobile to lower temperatures, freezing out at the lower transition. Physical aging is observed at a temperature below the upper transition, but above the lower transition, indicative of the upper transition being an actual glass transition associated with the α‐relaxation. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 64–75 相似文献
18.
Shing TK Cheng HM Wong WF Kwong CS Li J Lau CB Leung PS Cheng CH 《Organic letters》2008,10(14):3145-3148
A pseudo-1,4'- N-linked disaccharide, pseudoacarviosin 5, was constructed via a key palladium-catalyzed coupling reaction of pseudoglycosyl chloride 8 (prepared from d-glucose via a novel direct intramolecular aldol addition in 12 steps) and pseudo-4-amino-4,6-dideoxy-alpha- d-glucose 9 (prepared from l-arabinose via an unusual trans-fused isoxazolidine-selective intramolecular nitrone-alkene cycloaddition in 11 steps). Pseudoacarviosin 5 has been shown to be a potent inhibitor of alpha-glucosidases, particularly the intestinal mucosal enzymes sucrase and glucoamylase of relevance to blood glucose control. 相似文献
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Failes TW Cullinane C Diakos CI Yamamoto N Lyons JG Hambley TW 《Chemistry (Weinheim an der Bergstrasse, Germany)》2007,13(10):2974-2982
We report a potential means of selectively delivering matrix metalloproteinase (MMP) inhibitors to target tumour sites by use of a bioreductively activated Co(III) carrier system. The carrier, comprising a Co(III) complex of the tripodal ligand tris(methylpyridyl)amine (tpa), was investigated with the antimetastatic MMP inhibitor marimastat (mmstH(2)). The X-ray crystal structure of [Co(mmst)(tpa)]ClO(4) x 4H(2)O was determined and two-dimensional NMR revealed the existence of two isomeric forms of the complex in solution. Electrochemical analysis showed that the reduction potential of the complex is suitable for it to be bioreductively activated at hypoxic tumour sites. In vitro assays confirmed the stability of the prodrug in solution prior to reduction and revealed very low cytotoxicity against A2780 cells. In vivo testing in mice showed a higher level of tumour-growth inhibition by the complex than by free marimastat. Both free marimastat and and its Co(III) complex increased metastasis in the model used, with the complex significantly more active. 相似文献