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951.
Firooznia F Cheung AW Brinkman J Grimsby J Gubler ML Hamid R Marcopulos N Ramsey G Tan J Wen Y Sarabu R 《Bioorganic & medicinal chemistry letters》2011,21(7):1933-1936
The highly potent but modestly selective N-(2-amino-4-methoxy-benzothiazol-7-yl)-N-ethyl-acetamide derivative 2 was selected as the starting point for the design of novel selective A2B antagonists, due to its excellent potency, and good drug-like properties. A series of compounds containing nonaromatic amides or ureas of five- or six-membered rings, and also bearing an m-trifluoromethyl-phenyl group (shown to impart superior potency) was prepared and evaluated for their selectivity against the A2A and A1 receptors. This work resulted in the identification of compound 30, with excellent potency and high selectivity against both A2A and A1 receptors. 相似文献
952.
Jamaluddin MF Bailey UM Tan NY Stark AP Schulz BL 《Protein science : a publication of the Protein Society》2011,20(5):849-855
Asparagine-linked glycosylation is a common and vital co- and post-translocational modification of diverse secretory and membrane proteins in eukaryotes that is catalyzed by the multiprotein complex oligosaccharyltransferase (OTase). Two isoforms of OTase are present in Saccharomyces cerevisiae, defined by the presence of either of the homologous proteins Ost3p or Ost6p, which possess different protein substrate specificities at the level of individual glycosylation sites. Here we present in vitro characterization of the polypeptide binding activity of these two subunits of the yeast enzyme, and show that the peptide-binding grooves in these proteins can transiently bind stretches of polypeptide with amino acid characteristics complementary to the characteristics of the grooves. We show that Ost6p, which has a peptide-binding groove with a strongly hydrophobic base lined by neutral and basic residues, binds peptides enriched in hydrophobic and acidic amino acids. Further, by introducing basic residues in place of the wild type neutral residues lining the peptide-binding groove of Ost3p, we engineer binding of a hydrophobic and acidic peptide. Our data supports a model of Ost3/6p function in which they transiently bind stretches of nascent polypeptide substrate to inhibit protein folding, thereby increasing glycosylation efficiency at nearby asparagine residues. 相似文献
953.
Francesca ParatiRoberto Altieri Alessandro EspositoArianna Lobianco Milva PepiLorenzo Montesi Tan Nair 《International biodeterioration & biodegradation》2011,65(1):160-163
The production of a substrate containing destoned olive mill solid waste for the cultivation of Agaricus bisporus (Lange) Imbach on an industrial scale was studied. A standard mushroom compost (C) mainly made from straw and poultry manure was compared with the experimental compost (EC) containing the same ingredients as (C) but with added olive mill solid waste (10.6% w/w). Microbial indicators such as counts of heterotrophic microbes and actinomycetes were higher in EC than in C. In addition, compost selectivity as indicated by higher mushroom yield and biological efficiency of EC was higher than that of C. Market quality of the mushrooms produced in both C and EC were comparable. These findings support our work that olive mill solid waste can be used safely in thermal composting process to produce a selective substrate for industrial-scale cultivation of A. bisporus. This study also demonstrates an environmentally sustainable system to manage solid waste from olive oil extraction processes thus overcoming environmental pollution brought about by irrational disposal of the waste on farm lands. 相似文献
954.
955.
Chen SB Tan JH Ou TM Huang SL An LK Luo HB Li D Gu LQ Huang ZS 《Bioorganic & medicinal chemistry letters》2011,21(3):1004-1009
Discovery of potent and selective ligands for telomeric G-quadruplex DNA is a challenging work. Through a combination approach of pharmacophore model construction, model validation, database virtual screening, chemical synthesis and interaction evaluation, we discovered and confirmed triaryl-substituted imidazole TSIZ01 to be a new telomeric G-quadruplex ligand with potent binding and stabilizing activity to G-quadruplex DNA, as well as a 8.7-fold selectivity towards telomeric G-quadruplex DNA over duplex DNA. 相似文献
956.
Chlorophyll a and primary production were studied in northern South China Sea during summer from 2007 to 2008. Microplankton dominated total phytoplankton biomass in the coast, while picoplankton dominated in the offshore. Algae bloom caused by Thalassionema nitzschioides was found at the subsurface of upwelling regions (D2, C2) in 2008, and maximum of phytoplankton abundance reached 1.58 × 106 ind L?1. Integrated primary production ranged from 189.3 to 976.2 mg m?2 d?1 in 2007, and ranged from 652.1 to 6601 mg m?2 d?1 in 2008. PP showed positive relationship with IPP (p < 0.01) and negative relationship with SST (p < 0.05). Coastal upwelling and Pearl River discharge sustained high PP, and played important role in regulating the phytoplankton biomass and production. 相似文献
957.
象山港不同养殖类型海域大型底栖动物群落比较研究 总被引:7,自引:2,他引:5
于2009年2月在象山港顶部海域分别对海带、牡蛎和鱼类网箱3种不同养殖区进行了大型底栖动物调查。调查共鉴定大型底栖动物73种,隶属8门12纲53科,以软体动物和环节动物为主。海带养殖区优势种有5种;牡蛎养殖区有4种;网箱养殖区有9种。海带、牡蛎和网箱养殖区大型底栖动物平均栖息密度分别为(132±71)个/m2、(94±91)个/m2和(210±132)个/m2;平均生物量分别为(26.51±11.06) g/m2、(53.03±61.94) g/m2和(108.80±73.56) g/m2。栖息密度和生物量不同养殖区和不同调查站位间差异显著。Tukey多重比较结果显示,栖息密度海带养殖区与牡蛎和网箱养殖区间均无显著差异,而牡蛎与鱼类网箱养殖区间存在显著差异;生物量海带养殖区与牡蛎养殖区间无显著差异,海带养殖区和牡蛎养殖区与网箱养殖区间均显著差异。典范对应分析结果表明,对大型底栖动物群落起主要影响的环境因子有温度、盐度、总氮和总磷等,排序轴对物种-环境关系的贡献率计算结果表明环境变量可以较好的解释主要类群的变化情况。丰度/生物量比较曲线(ABC曲线)分析结果表明,网箱养殖区大型底栖动物群落受较明显扰动,而海带和牡蛎养殖区大型底栖动物群落未受扰动。 相似文献
958.
Chen SY Chen Y Li YP Chen SH Tan JH Ou TM Gu LQ Huang ZS 《Bioorganic & medicinal chemistry》2011,19(18):5596-5604
A series of novel curcumin analogues were designed, synthesized, and evaluated as potential multifunctional agents for the treatment of AD. The in vitro studies showed that these compounds had better inhibitory properties against Aβ aggregation than curcumin. Superior anti-oxidant properties (better than the reference compound Trolox) of these compounds were observed by the oxygen radical absorbance capacity (ORAC) method and a cell-based assay using DCFH-DA as a probe. In addition they were able to chelate metals such as iron and copper and decrease metal-induced Aβ aggregation. The structure-activity relationships were discussed. The results suggested that our curcumin analogues could be selected as multifunctional agents for further investigation of AD treatment. 相似文献
959.
Li Y Tan C Gao C Zhang C Luan X Chen X Liu H Chen Y Jiang Y 《Bioorganic & medicinal chemistry》2011,19(15):4529-4535
Multi-target EGFR, VEGFR-2 and PDGFR inhibitors are highly useful anticancer agents with improved therapeutic efficacies. In this work, we used two virtual screening methods, support vector machines (SVM) and molecular docking, to identify a novel series of benzimidazole derivatives, 2-aryl benzimidazole compounds, as multi-target EGFR, VEGFR-2 and PDGFR inhibitors. 2-Aryl benzimidazole compounds were synthesized and their biological activities against a tumor cell line HepG-2 and specific kinases were evaluated. Among these compounds, compounds 5a and 5e exhibited high cytotoxicity against HepG-2 cells with IC?? values at ~2 μM. Further kinase assay study showed that compound 5a have good EGFR inhibitory activity and moderate VEGFR-2 and PDGFR inhibitory activities, while 5e have moderate EGFR inhibitory activity and slightly weaker VEGFR-2 and PDGFR inhibitory activities. Molecular docking analysis suggested that compound 5a more tightly interacts with EGFR and PDGFR than compound 5e. Our study discovered a novel series of benzimidazole derivatives as multi-target EGFR, VEGFR-2 and PDGFR kinases inhibitors. 相似文献
960.
Ge X McFarlane C Vajjala A Lokireddy S Ng ZH Tan CK Tan NS Wahli W Sharma M Kambadur R 《Cell research》2011,21(11):1591-1604
TGF-β and myostatin are the two most important regulators of muscle growth. Both growth factors have been shown to signal through a Smad3-dependent pathway. However to date, the role of Smad3 in muscle growth and differentiation is not investigated. Here, we demonstrate that Smad3-null mice have decreased muscle mass and pronounced skeletal muscle atrophy. Consistent with this, we also find increased protein ubiquitination and elevated levels of the ubiquitin E3 ligase MuRF1 in muscle tissue isolated from Smad3-null mice. Loss of Smad3 also led to defective satellite cell (SC) functionality. Smad3-null SCs showed reduced propensity for self-renewal, which may lead to a progressive loss of SC number. Indeed, decreased SC number was observed in skeletal muscle from Smad3-null mice showing signs of severe muscle wasting. Further in vitro analysis of primary myoblast cultures identified that Smad3-null myoblasts exhibit impaired proliferation, differentiation and fusion, resulting in the formation of atrophied myotubes. A search for the molecular mechanism revealed that loss of Smad3 results in increased myostatin expression in Smad3-null muscle and myoblasts. Given that myostatin is a negative regulator, we hypothesize that increased myostatin levels are responsible for the atrophic phenotype in Smad3-null mice. Consistent with this theory, inactivation of myostatin in Smad3-null mice rescues the muscle atrophy phenotype. 相似文献