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31.
Xianfeng Li Yang Liu Yong-Kang Zhang Jacob J. Plattner Stephen J. Baker Wei Bu Liang Liu Yasheen Zhou Charles Z. Ding Suoming Zhang Wieslaw M. Kazmierski Robert Hamatake Maosheng Duan Lois L. Wright Gary K. Smith Richard L. Jarvest Jing-Jing Ji Joel P. Cooper Matthew D. Tallant Renae M. Crosby Amy Wang 《Bioorganic & medicinal chemistry letters》2012,22(24):7351-7356
We have synthesized and evaluated a series of novel HCV NS3 protease inhibitors with various P4 capping groups, which include urea, carbamate, methoxy-carboxamide, cyclic carbamate and amide, pyruvic amide, oxamate, oxalamide and cyanoguanidine. Most of these compounds are remarkably potent, exhibiting single-digit to sub-nanomolar activity in the enzyme assay and cell-based replicon assay. Selected compounds were also evaluated in the protease-inhibitor-resistant mutant transient replicon assay, and they were found to show quite different potency profiles against a panel of HCV protease-inhibitor-resistant mutants. 相似文献
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Wintjens R Wieruszeski JM Drobecq H Rousselot-Pailley P Buée L Lippens G Landrieu I 《The Journal of biological chemistry》2001,276(27):25150-25156
The recent crystal structure of Pin1 protein bound to a doubly phosphorylated peptide from the C-terminal domain of RNA polymerase II revealed that binding interactions between Pin1 and its substrate take place through its Trp-Trp (WW) domain at the level of the loop Ser(11)-Arg(12) and the aromatic pair Tyr(18)-Trp(29), and showed a trans conformation for both pSer-Pro peptide bonds. However, the orientation of the ligand in the aromatic recognition groove still could be sequence-specific, as previously observed in SH3 domains complexed by peptide ligands or for different class of WW domains (Zarrinpar, A., and Lim, W. A. (2000) Nat. Struct. Biol. 7, 611-613). Because the bound peptide conformation could also differ as observed for peptide ligands bound to the 14-3-3 domain, ligand orientation and conformation for two other biologically relevant monophosphate substrates, one derived from the Cdc25 phosphatase of Xenopus laevis (EQPLpTPVTDL) and another from the human tau protein (KVSVVRpTPPKSPS) in complex with the WW domain are here studied by solution NMR methods. First, the proton resonance perturbations on the WW domain upon complexation with both peptide ligands were determined to be essentially located in the positively charged beta-hairpin Ser(11)-Gly(15) and around the aromatic Trp(29). Dissociation equilibrium constants of 117 and 230 microm for Cdc25 and tau peptides, respectively, were found. Several intermolecular nuclear Overhauser effects between WW domain and substrates were obtained from a ligand-saturated solution and were used to determine the structures of the complexes in solution. We found a similar N to C orientation as the one observed in the crystal complex structure of Pin1 and a trans conformation for the pThr-Pro peptidic bond in both peptide ligands, thereby indicating a unique binding scheme for the Pin1 WW domain to its multiple substrates. 相似文献
34.
Plant Ecology - Knowledge of the responses of climbing plants to disturbance is important in understanding the ecology of climber but still lacking a general agreement. The present study quantified... 相似文献
35.
Solar Cells: Synergic Interface Optimization with Green Solvent Engineering in Mixed Perovskite Solar Cells (Adv. Energy Mater. 20/2017) 下载免费PDF全文
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In order to further understand the coordination chemistry of diazamesocyclic systems, a series of mononuclear NiII complexes with 1,4-diazacycloheptane (DACH) functionalized by additional imidazole or pyridine donor pendants, including [NiL1](ClO4)2 · H2O (1), [NiL1Cl](ClO4) (2), [NiL2Cl](ClO4) · CH3OH (3), [NiL2Cl][NiL2](ClO4)3 (4) and [NiL3](ClO4)2 (5), where L1 = 1,4-bis(N-1-methylimidazol-2-yl-methyl)-1,4-diazacycloheptane, L2 = 1,4-bis(pyridyl-2-yl-methyl)-1,4-diazacycloheptane, and L3 = 1,4-bis-(imidazol-4-yl-methyl)-1,4-diazacycloheptane, have been prepared and characterized. A detailed study on the solid structures and solution spectra of these complexes indicates that tetradentate ligands L1, L2 and L3 would lead to new NiII complexes with different coordination environments in the solid states and solution. The N-methyl substituted imidazole functionalized ligand L1 forms green compound 2 and yellow product 1; while the pyridine functionalized ligand L2 affords red product 4 and green complex 3; the ligand L3 results in only one stable mononuclear NiII product 5. The solution behaviors of these interesting compounds were also investigated by UV-Vis technique. 相似文献
38.
Ska2(spindle and kinetochore associated complex subunit2),又称FAM33A(family with sequence similarity33,member A),是新近发现的一个与细胞周期调控和肿瘤发生发展紧密相关的基瓯且与该团队前期发现的新基NPRR11(proline rich 11)共享一个双向启动子。但是,Ska2在肺癌中的具体作用和分子机制仍不清楚。该研究选用肺癌细胞系H1299,采用RNAi技术构建Ska2基因沉默的稳定细胞株,并进行了细胞表型和潜在分子机制分析。RT-PCR和Western blot结果表明,Ska2在mRNA和蛋白质水平上的表达均被有效抑制。细胞增殖、细胞迁移和侵袭实验结果表明,与对照细胞相比,Ska2基因沉默稳定细胞株的细胞增殖能力、细胞迁移和侵袭能力均显著降低。此外,Ska2基因被沉默后,CCNA1基因的表达显著下调。该研究的结果提示,Ska2与其对侧基因PRR11的功能高度相关,可能与PRR11共同参与肺癌细胞增殖、迁移和侵袭行为的调节。 相似文献
39.
Katarína Šoltys Matej Planý Paola Biocca Valentina Vianello Mária Bučková Andrea Puškárová Maria Carla Sclocchi Piero Colaizzi Marina Bicchieri Domenico Pangallo Flavia Pinzari 《Environmental microbiology》2020,22(4):1517-1534
A multidisciplinary approach was carried out in order to study the biodeterioration and the associated microbiome of a XVIII Century wax seal coloured with minium. A small wax seal fragment was observed by scanning electron microscopy combined with energy dispersive spectroscopy in non-destructive mode. The same object was analysed by Raman and Fourier-transform infrared spectroscopy. The identification of the microbiota growing on the seal was performed with both a culture-dependent strategy, combined with hydrolytic assays, and high-throughput sequencing using the MinION platform. The whole bacterial 16S rRNA gene and the fungal markers ITS and 28S rRNA were targeted. It was observed that the carnauba wax coloured with lead tetroxide (minium) was covered by a biofilm consisting of a network of filaments and other structures of microbial origin. The culture-dependent and culture-independent investigations showed the presence of a complex microbiota composed mainly by fungal members, which demonstrated interesting properties related to lipids and lead processing. The formation of lead soaps and secondary biogenic minerals was also described. 相似文献
40.
Jun Hong Xia Grace Lin Xiaoping He Bu Yunping Peng Liu Feng Liu Fei Sun Rongjian Tu Gen Hua Yue 《Marine biotechnology (New York, N.Y.)》2014,16(1):1-9
Omega-3 fatty acids are essential fatty acids for human health. Therefore, increasing both percentage of omega-3 and a better fatty acid profile in fish fillets is one of the breeding goals in aquaculture. However, it is difficult to increase the omega-3 content in fish fillets, as the phenotypic selection of these traits is not easily feasible. To facilitate the genetic improvement of the Asian seabass for optimal fatty acid profiles, a genome-wide scan for quantitative trait loci (QTL) affecting fatty acid level in the flesh of the Asian seabass was performed on an F2 family containing 314 offspring. All family members were genotyped using 123 informative microsatellites and 22 SNPs. High percentages of n-3 polyunsaturated fatty acids (PUFA), especially C22:6 (DHA 16.48?±?3.09 %) and C20:5 (EPA 7.19?±?0.86 %) were detected in the flesh. One significant and 54 suggestive QTL for different fatty acids and a water content trait were detected on the whole genome. QTL for C18:0b was located on linkage groups (LG) 5. QTL for total n-3 PUFA content in flesh were mapped onto LG6 and LG23 with the phenotypic variance explained ranging from 3.8 to 6.3 %. Four QTL for C22:6 were detected on LG6, LG23, and LG24, explaining 3.9 to 4.9 % of the phenotypic variance, respectively. Mapping of QTL for contents of different fatty acids is the first step towards improving the omega-3 content in the fillets of fish by using marker-assisted selection and is important for understanding the biology of fatty acid deposition. 相似文献