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排序方式: 共有214条查询结果,搜索用时 31 毫秒
31.
Anil Kumar Podichetty Andreas Faust Klaus Kopka Stefan Wagner Otmar Schober Michael Schäfers Günter Haufe 《Bioorganic & medicinal chemistry》2009,17(7):2680-2688
A series of new N-substituted (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives has been synthesized and tested as inhibitors of caspases-3 and -7, which are known to be downstream enzymes critical in the execution of apoptosis. N-Propyl- and N-butyl isatins, as well as the corresponding terminal alcohols and regioisomeric fluorobutyl derivatives were shown to be excellent inhibitors having different binding potencies for caspases-3 and -7. In contrast, the corresponding fluoroethyl and fluoropropyl compounds were about 100–1000 times less active. Fluorinated N-benzyl isatins as well as trifluoroalkyl and difluoroalkyl derivatives were moderate inhibitors. However, isatins bearing different alkylether groups at N-1 are very weak or not active as inhibitors of caspases-3 and -7. 相似文献
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Höltke C Law MP Wagner S Breyholz HJ Kopka K Bremer C Levkau B Schober O Schäfers M 《Bioorganic & medicinal chemistry》2006,14(6):1910-1917
It is assumed that the regulation of cardiac endothelin (ET) receptor density is abnormal in heart diseases. From that perspective, an ET receptor radioligand is needed to assess ET receptor density in vivo. The nonpeptidyl ET(A) receptor antagonist PD 169390 was labelled with radioiodine to give a putative radioligand for SPECT. Labelling with [125I]iodide and [123I]iodide was accomplished with good to excellent radiochemical yields. The affinities of the nonradioactive reference and those of selected precursor compounds for ET(A) receptors were determined, using [125I]iodine labelled endothelin-1 with mouse ventricular membranes. All employed substances exhibited potent in vitro pharmacological characteristics with Ki values comparable to that of the lead compound PD 156707. Biodistribution studies and scintigraphic imaging experiments in mice, however, showed no significant uptake of the [123I] derivative in the heart. 相似文献
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Kienesberger S Schober Trummler C Fauster A Lang S Sprenger H Gorkiewicz G Zechner EL 《Journal of bacteriology》2011,193(3):744-758
We report here the first demonstration of intra- and interspecies conjugative plasmid DNA transfer for Campylobacter fetus. Gene regions carried by a Campylobacter coli plasmid were identified that are sufficient for conjugative mobilization to Escherichia coli and C. fetus recipients. A broader functional range is predicted. Efficient DNA transfer involves the virB9 and virD4 genes of the type IV bacterial secretion system encoded by a pathogenicity island of C. fetus subsp. venerealis. Complementation of these phenotypes from expression constructions based on the promoter of the C. fetus surface antigen protein (sap) locus was temperature dependent, and a temperature regulation of the sap promoter was subsequently confirmed under laboratory conditions. Gene transfer was sensitive to surface or entry exclusion functions in potential recipient cells carrying IncPα plasmid RP4 implying functional relatedness to C. fetus proteins. The virB/virD4 locus is also known to be involved in bacterial invasion and killing of cultured human cells in vitro. Whether specifically secreted effector proteins contribute to host colonization and infection activities is currently unknown. Two putative effector proteins carrying an FIC domain conserved in a few bacterial type III and type IV secreted proteins of pathogens were analyzed for secretion by the C. fetus or heterologous conjugative systems. No evidence for interbacterial translocation of the Fic proteins was found. 相似文献
36.
Jiang Wei Marcus Freytag Yvonne Schober Wolfgang A. Nockher Victor F. Mautner Reinhard E. Friedrich Paul W. Manley Lan Kluwe Andreas Kurtz 《PloS one》2014,9(10)
Plexiform neurofibromas (PNFs) are benign nerve sheath tumors mostly associated with neurofibromatosis type 1. They often extend through multiple layers of tissue and therefore cannot be treated satisfactorily by surgery. Nilotinib is a tyrosine kinase inhibitor used to treat leukemia, with advantages over the prototype imatinib in terms of potency and selectivity towards BCR-ABL, and the DDR, PDGFR, and KIT receptor kinases. In this study, we compared efficacies of the two drugs on cultured cells of PNF in vitro and on xenografted tumor fragments on sciatic nerve of athymic nude mice. Xenografts were monitored weekly using a high resolution ultrasound measurement. Treatment with nilotinib at a daily dose of 100 mg/kg for four weeks led to a reduction of the graft sizesstd by 68±7% in the 8 treated mice, significantly more than the 33±8% reduction in the 8 untreated mice (P<0.05) and the 47±15% in the 7 mice treated with imatinib (P<0.05). The peak plasma nilotinib concentration 6.6±1.1 µM is within the pharmacological range of clinical application. Imatinib, but not nilotinib significantly hindered body weight increase of the mice and elevated cytotoxicity of mouse spleen cells (P<0.05). Our results suggest that nilotinib may be more potent than imatinib for treating PNFs and may also be better tolerated. Imatinib seems to have some off-target effect in elevating immunity. 相似文献
37.
Overlapping genes are two protein-coding sequences sharing a significant part of the same DNA locus in different reading frames. Although in recent times an increasing number of examples have been found in bacteria the underlying mechanisms of their evolution are unknown. In this work we explore how selective pressure in a protein-coding sequence influences its overlapping genes in alternative reading frames. We model evolution using a time-continuous Markov process and derive the corresponding model for the remaining frames to quantify selection pressure and genetic noise. Our findings lead to the presumption that, once information is embedded in the reverse reading frame −2 (relative to the mother gene in +1) purifying selection in the protein-coding reading frame automatically protects the sequences in both frames. We also found that this coincides with the fact that the genetic noise measured using the conditional entropy is minimal in frame −2 under selection in the coding frame. 相似文献
38.
Yan Lu Shulin/SL Li Shiguo/SG Zhu Yabin/YB Gong Jun/J Shi Ling/ L Xu 《Biological procedures online》2017,19(1):2
DNA/RNA methylation plays an important role in lung cancer initiation and progression. Liquid biopsy makes use of cells, nucleotides and proteins released from tumor cells into body fluids to help with cancer diagnosis and prognosis. Methylation of circulating tumor DNA (ctDNA) has gained increasing attention as biomarkers for lung cancer. Here we briefly introduce the biological basis and detection method of ctDNA methylation, and review various applications of methylated DNA in body fluids in lung cancer screening, diagnosis, prognosis, monitoring and treatment prediction. We also discuss the emerging role of RNA methylation as biomarkers for cancer. 相似文献
39.
W Schober 《Zeitschrift für mikroskopisch-anatomische Forschung》1983,97(3):409-426
The afferent and efferent connections of the Corpus geniculatum laterale, pars ventralis (Cglv) of the albino rat were investigated lightmicroscopically by using either silver degeneration methods and the HRP-method as well. In contrast to the dorsal Cgl the results show remarkably different afferent connections in the ventral Cgl. The afferent fibres originate from the following areas: a) Retina: the terminal degeneration area of optic fibres includes the lateral part of the Cglv only. b) Regio praetectalis: degenerating fibres from these region can also be observed in the medial part of the Cglv. c) Colliculus superior: degenerating fibres terminate mainly in the lateral part of the Cglv. In the superior colliculus these fibres originate particularly from the cells of lamina III. d) Visual cortex: neurons of layer V of area 17 project mainly to the lateral half of the Cglv. There was no evidence for a projecting of the parastriate cortex (area 18 a) to the Cglv. The efferent fibres reach the following target areas: a) Nucleus lateralis posterior, Regio praetectalis and Colliculus superior. Evidence for a projection to the dorsal Cgl requires further investigation. b) Zona incerta, Formatio reticularis mesencephali and Nucleus medialis et lateralis pontis. Neurons in the medial half ot eh Cglv project to the pons region. c) Crossing the Commissura posterior and the Commissura suprachiasmatica, efferent fibres reach the contralateral Cglv, the Regio praetectalis and the Colliculus superior. The results obtained from the rat are compared with findings from other mammalian species. The functional importance of the Cglv in the visual processes is discussed taking into consideration the specific connections. 相似文献
40.
Twenty-nine flavonoid aglycones have been identified from two populations each of Heterotheca grandiflora and H. psammophila. Considerable qualitative variation was found between populations of the same species. Overall, H. grandiflora is more complex in its flavonoid profile, accumulating a total of 24 compounds based on eight skeletal types, compared with 13 compounds based on four skeletal types in H. psammophila. 相似文献