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排序方式: 共有128条查询结果,搜索用时 703 毫秒
71.
Angell A McGuigan C Garcia Sevillano L Snoeck R Andrei G De Clercq E Balzarini J 《Bioorganic & medicinal chemistry letters》2004,14(10):2397-2399
Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family bearing a p-alkylphenyl side chain have been synthesised and tested for their antiviral activity against Varicella-Zoster virus (VZV). While the alkyl chain analogues were shown to retain full antiviral activity against VZV, these new analogues did not when compared to their furo parent nucleosides. 相似文献
72.
Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach 总被引:18,自引:0,他引:18
Angell JE Lindner DJ Shapiro PS Hofmann ER Kalvakolanu DV 《The Journal of biological chemistry》2000,275(43):33416-33426
We show here that the combination of interferon-beta (IFN-beta) and all-trans-retinoic acid (RA) induces the death of tumor cells. To understand the molecular basis for synergistic growth-suppressive action and to identify the gene products that participate in this process, we have employed an antisense knock-out technique. This approach permits the isolation of cell death-associated genes based on their selective inactivation by overexpression of antisense cDNAs. Because the antisense mRNA inactivates gene expression of death-specific genes, transfected cells survive in the presence death inducers. Several Genes associated with Retinoid-IFN-induced Mortality (GRIM) were identified using this approach. Here we report the isolation of a novel GRIM gene, GRIM-19. This 552-base pair cDNA encodes a 16-kDa protein. Antisense expression of GRIM-19 confers a strong resistance against IFN/RA-induced death by reducing the intracellular levels of GRIM-19 protein. Overexpression of GRIM-19 enhances cell death in response to IFN/RA. GRIM-19 is primarily a nuclear protein whose expression is induced by the IFN/RA combination. Together, our studies identify a novel cell death-regulatory molecule. 相似文献
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Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation
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Mariano Barbieri Benjamin L Moore Dorothee CA Kraemer Stuart Aitken Sheila Q Xie Kelly J Morris Masayoshi Itoh Hideya Kawaji Ines Jaeger Yoshihide Hayashizaki Piero Carninci Alistair RR Forrest The FANTOM Consortium Colin A Semple Josée Dostie Ana Pombo Mario Nicodemi 《Molecular systems biology》2015,11(12)
75.
Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus interacts with a cell death regulator,GRIM19, and inhibits interferon/retinoic acid-induced cell death 总被引:8,自引:0,他引:8
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![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Seo T Lee D Shim YS Angell JE Chidambaram NV Kalvakolanu DV Choe J 《Journal of virology》2002,76(17):8797-8807
76.
Kotaka M Dhaliwal B Ren J Nichols CE Angell R Lockyer M Hawkins AR Stammers DK 《Protein science : a publication of the Protein Society》2006,15(4):774-784
Methicillin-resistant Staphylococcus aureus (MRSA) poses a major threat to human health, particularly through hospital acquired infection. The spread of MRSA means that novel targets are required to develop potential inhibitors to combat infections caused by such drug-resistant bacteria. Thymidylate kinase (TMK) is attractive as an antibacterial target as it is essential for providing components for DNA synthesis. Here, we report crystal structures of unliganded and thymidylate-bound forms of S. aureus thymidylate kinase (SaTMK). His-tagged and untagged SaTMK crystallize with differing lattice packing and show variations in conformational states for unliganded and thymidylate (TMP) bound forms. In addition to open and closed forms of SaTMK, an intermediate conformation in TMP binding is observed, in which the site is partially closed. Analysis of these structures indicates a sequence of events upon TMP binding, with helix alpha3 shifting position initially, followed by movement of alpha2 to close the substrate site. In addition, we observe significant conformational differences in the TMP-binding site in SaTMK as compared to available TMK structures from other bacterial species, Escherichia coli and Mycobacterium tuberculosis as well as human TMK. In SaTMK, Arg 48 is situated at the base of the TMP-binding site, close to the thymine ring, whereas a cis-proline occupies the equivalent position in other TMKs. The observed TMK structural differences mean that design of compounds highly specific for the S. aureus enzyme looks possible; such inhibitors could minimize the transfer of drug resistance between different bacterial species. 相似文献
77.
Angell RM Angell TD Bamborough P Brown D Brown M Buckton JB Cockerill SG Edwards CD Jones KL Longstaff T Smee PA Smith KJ Somers DO Walker AL Willson M 《Bioorganic & medicinal chemistry letters》2008,18(1):324-328
The biphenyl amides are a novel series of p38 MAP kinase inhibitors. Structure-activity relationships of the series against p38alpha are discussed with reference to the X-ray crystal structure of an example. The series was optimised rapidly to a compound showing oral activity in an in vivo disease model. 相似文献
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Lombardi PM Angell HD Whittington DA Flynn EF Rajashankar KR Christianson DW 《Biochemistry》2011,50(11):1808-1817
Polyamines are a ubiquitous class of polycationic small molecules that can influence gene expression by binding to nucleic acids. Reversible polyamine acetylation regulates nucleic acid binding and is required for normal cell cycle progression and proliferation. Here, we report the structures of Mycoplana ramosa acetylpolyamine amidohydrolase (APAH) complexed with a transition state analogue and a hydroxamate inhibitor and an inactive mutant complexed with two acetylpolyamine substrates. The structure of APAH is the first of a histone deacetylase-like oligomer and reveals that an 18-residue insert in the L2 loop promotes dimerization and the formation of an 18 ? long "L"-shaped active site tunnel at the dimer interface, accessible only to narrow and flexible substrates. The importance of dimerization for polyamine deacetylase function leads to the suggestion that a comparable dimeric or double-domain histone deacetylase could catalyze polyamine deacetylation reactions in eukaryotes. 相似文献