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961.
A distant upstream locus control region is critical for expression of the Kit receptor gene in mast cells
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Berrozpe G Agosti V Tucker C Blanpain C Manova K Besmer P 《Molecular and cellular biology》2006,26(15):5850-5860
The Kit receptor tyrosine kinase functions in hematopoiesis, melanogenesis, and gametogenesis and in interstitial cells of Cajal. We previously identified two upstream hypersensitive site (HS) clusters in mast cells and melanocytes. Here we investigated the roles of these 5' HS sequences in Kit expression using transgenic mice carrying Kit-GFP reporter constructs. In these mice there is close correspondence between Kit-GFP reporter and endogenous Kit gene expression in most tissues analyzed. Deletion analysis defined the 5' upstream HS cluster region as critical for Kit expression in mast cells. Furthermore, chromatin immunoprecipitation analysis in mast cells showed that H3 and H4 histone hyperacetylation and RNA polymerase II recruitment within the Kit promoter and in the 5' HS region were associated with Kit expression. Therefore, the 5' upstream hypersensitivity sites appear to be critical components of locus control region-mediated Kit gene activation in mast cells. 相似文献
962.
Baraldi PG Pavani MG Leung E Moorman AR Varani K Vincenzi F Borea PA Romagnoli R 《Bioorganic & medicinal chemistry letters》2006,16(5):1402-1404
Among the adenosine A(1) allosteric enhancers reported so far, compound (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)-(4-chlorophenyl)-methanone 1 (named T-62) has shown biological properties similar to those of PD 81,723, the reference A(1) allosteric enhancer and it has been more fully pharmacologically investigated. The preparation of the radiolabelled form of compound 1 and its characterization by saturation binding experiments are reported. These studies allowed us to demonstrate for the first time the existence of a specific, allosteric site on the A(1) receptor. 相似文献
963.
Romagnoli R Baraldi PG Moorman AR Iaconinoto MA Carrion MD Cara CL Tabrizi MA Preti D Fruttarolo F Baker SP Varani K Borea PA 《Bioorganic & medicinal chemistry letters》2006,16(21):5530-5533
The microwave-assisted aromatization method has been used for the synthesis of a series of novel thieno[2,3-c]pyridines. This rapid method produces compounds in good yield within minutes in comparison with conventional heating method. The synthesized molecules have been evaluated as a potential new series of allosteric enhancers acting at the adenosine A(1) receptor. In a functional assay, one compound (3h) showed activity comparable with that of reference compound PD 81,723. 相似文献
964.
965.
966.
Purification and biochemical characterization of a monomeric form of papaya mosaic potexvirus coat protein 总被引:1,自引:0,他引:1
Lecours K Tremblay MH Gagné ME Gagné SM Leclerc D 《Protein expression and purification》2006,47(1):273-280
Papaya mosaic virus (PapMV) is a flexuous rod shape virus made of 1400 subunits that assemble around a plus sense genomic RNA. The structure determination of PapMV and of flexuous viruses in general is a major challenge for both NMR and X-ray crystallography. In this report, we present the characterization of a truncated version of the PapMV coat protein (CP) that is suitable for NMR study. The deletion of the N-terminal 26 amino acids of the PapMV CP (CP27-215) generates a monomer that can be expressed to high level and easily purified for production of an adequate NMR sample. The RNA gel shift assay showed that CP27-215 lost its ability to bind RNA in vitro, suggesting that the multimerization of the subunit is important for this function. The fusion of a 6x His tag at the C-terminus improved the solubility of the monomer and allowed its concentration to 0.2 mM. The CD spectra of the truncated and the wild-type proteins were similar, suggesting that both proteins are well ordered and have a similar secondary structure. CP27-215 was 15N labeled for NMR studies and a 2D 1H-15N-HSQC spectrum confirmed the presence of a well-ordered structure and the monomeric form of the protein. These results show that CP27-215 is amenable to a complete and exhaustive NMR study that should lead to the first three-dimensional structure determination of a flexuous rod shape virus. 相似文献
967.
Background
We recently observed an association of resistance with a certain enteropathogenic Escherichia coli (EPEC) serotypes and identified a conjugative plasmid, similar to plasmid pED208, that was conserved among archival O111:H2/NM and O119:H2 strains of diverse geographical origin. In this study, we sought to determine the prevalence and distribution of this plasmid among a collection of EPEC isolates from Brazil, as well as to study the susceptibilities of these isolates to antimicrobial agents. 相似文献968.
969.
Pamela Crepaldi Barbara Cacciari Maria-Cruz Bonache Giampiero Spalluto Katia Varani Pier Andrea Borea Ivar von Kügelgen Kristina Hoffmann Mariateresa Pugliano Cristina Razzari Marco Cattaneo 《Bioorganic & medicinal chemistry》2009,17(13):4612-4621
P2Y12 plays an important role in platelet aggregation, which makes it an interesting target for antithrombotic agents. Compounds that antagonize P2Y12 include the active metabolites of thienopyridines and molecules that are structurally related to ATP, which is an antagonist of P2Y12. During the last few years, our group has been working on the development of P2Y12 receptors antagonists that are based on an extremely simple chemical structure, the 6-amino-2-mercapto-3H-pyrimidin-4-one, variously substituted at the sulfur and oxygen functions. This nucleus represents the simplified combination of two known P2Y12 antagonists: the active metabolite of the thienopyridines and ATP derivatives. The effects of the synthesized compounds were tested on ADP-induced human platelet aggregation, using light transmission aggregometry. None of the tested compounds induced platelet aggregation, while some of them, at concentration of 10?4 M, partially inhibited platelet aggregation induced by ADP 10?6 M. The most potent compound, 6b, antagonized the inhibitory effect of 2-methylthio-ADP on the forskolin-induced accumulation of cyclic-AMP in CHO FlpIN cells expressing recombinant human P2Y12-receptors. In addition, none of the tested compounds, including 6b, interfered with ligand binding to P1 receptors. Our results suggest that some of the synthesized compounds are specific antagonists of P2 receptors, and in particular of P2Y12 and suggest that further development of this structurally new series of compounds as P2Y12 receptors antagonists is recommended. 相似文献
970.