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排序方式: 共有1346条查询结果,搜索用时 31 毫秒
41.
The Fight against the Influenza A Virus H1N1: Synthesis,Molecular Modeling,and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors 下载免费PDF全文
Dr. Mafalda Pagano Dr. Daniele Castagnolo Dr. Martina Bernardini Anna Lucia Fallacara Ilaria Laurenzana Davide Deodato Dr. Ulrich Kessler Dr. Beatrice Pilger Dr. Lilli Stergiou Dr. Stephan Strunze Dr. Cristina Tintori Prof. Maurizio Botta 《ChemMedChem》2014,9(1):129-150
The influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed between subunits PA and PB1. Docking studies were also performed to elucidate the binding mode of benzofurazans within the PB1 binding site in PA and to identify amino acids involved in their mechanism of action. The predicted binding pose is fully consistent with the biological data and lays the foundation for the rational development of more effective PA–PB1 inhibitors. 相似文献
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选取来源于大肠杆菌O157: H7全基因组DNA序列随机转录的3条RNA片段,通过RNAComposer进行结构预测,30个核苷酸的RNA片段均形成了特定的空间结构,构象与碱基排列的序列特异性有关。 NPDock可用于RNA-蛋白质相互作用的分子模拟预测,蛋白质的β-结构相对α-螺旋更容易裸露出特定氨基残基的特异性侧链基团,从而易于结合抗原等配体。 相似文献
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Zhong-Tao Ding Zhi Zhang Di Luo Jin-Yan Zhou Juan Zhong Jie Yang Liang Xiao Dan Shu Hong Tan 《International journal of molecular sciences》2015,16(5):10301-10323
The phytopathogenic ascomycete Botrytis cinerea produces several secondary metabolites that have biotechnical significance and has been particularly used for S-(+)-abscisic acid production at the industrial scale. To manipulate the expression levels of specific secondary metabolite biosynthetic genes of B. cinerea with Agrobacterium tumefaciens-mediated transformation system, two expression vectors (pCBh1 and pCBg1 with different selection markers) and one RNA silencing vector, pCBSilent1, were developed with the In-Fusion assembly method. Both expression vectors were highly effective in constitutively expressing eGFP, and pCBSilent1 effectively silenced the eGFP gene in B. cinerea. Bcaba4, a gene suggested to participate in ABA biosynthesis in B. cinerea, was then targeted for gene overexpression and RNA silencing with these reverse genetic tools. The overexpression of bcaba4 dramatically induced ABA formation in the B. cinerea wild type strain Bc-6, and the gene silencing of bcaba4 significantly reduced ABA-production in an ABA-producing B. cinerea strain. 相似文献
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Xiaoshuang Liu Guangxin Zhang Changqing Zhang Jin Wang 《International journal of molecular sciences》2015,16(2):3377-3390
Endogenous small non-coding RNAs play pivotal roles in regulating gene expression in eukaryotes. Many studies have investigated the function and molecular mechanism of microRNAs in the development and disease of various organisms via mRNA repression of protein-coding genes. Recent findings indicate microRNAs might trigger the generation of trans-acting small interfering RNAs (ta-siRNAs). The interaction among different types of small RNA molecules reveals an even more complicated and elaborate pattern of RNA regulation during gene expression than previously thought. We developed a method for mining ta-siRNA sequences and evaluated the performance of our novel method using data from Arabidopsis thaliana. Additionally, using small RNA and degradome data for the human brain, we identified 155 small RNAs that satisfied ta-siRNA characteristics. The DRAXIN and ATCAY genes, which are preferentially expressed in the human brain, were predicted to be the targets of 12 potential ta-siRNAs. 相似文献
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Yajing Mi Xingchun Gao Jinxiang Dai Yue Ma Lixian Xu Weilin Jin 《International journal of molecular sciences》2015,16(9):21846-21857
DNA dioxygenases Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), and thereby alter the epigenetic state of DNA. The TET family includes TET1, TET2 and TET3 members in mammals. Recently, accumulative research uncovered that TET1–3 occur abundantly in the central nervous system (CNS), and their biological functions have just begun to be investigated. In the present study, we demonstrated that mRNA and protein of TET2 were highly expressed in the cerebral cortex and hippocampus along the whole brain-development process. Further studies showed that TET2 was expressed in various types of cells, especially in most neurons. Subcellular distribution pattern implicated that TET2 is localized in both nucleus and cytoplasm of neurons. Down-regulation of TET2 in cultured cortical neurons with RNA interference implied that TET2 was required for cell survival. In all, our results indicate that neuronal TET2 is positively involved in the regulation of cell survival. 相似文献
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pH‐Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid‐Based Delivery Systems 下载免费PDF全文
Dr. Khalid Oumzil Sébastien Benizri Giovanni Tonelli Dr. Cathy Staedel Ananda Appavoo Max Chaffanet Laurence Navailles Prof. Philippe Barthélémy 《ChemMedChem》2015,10(11):1797-1801
Lipid‐based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3′‐orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH‐sensitive liposomes. ONL‐based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH‐cleavable nucleolipids to control the stability of lipid‐based delivery systems represents a promising approach for the intracellular delivery of drug cargos. 相似文献
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