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排序方式: 共有94条查询结果,搜索用时 15 毫秒
41.
Michelotti EL Moffett KK Nguyen D Kelly MJ Shetty R Chai X Northrop K Namboodiri V Campbell B Flynn GA Fujimoto T Hollinger FP Bukhtiyarova M Springman EB Karpusas M 《Bioorganic & medicinal chemistry letters》2005,15(23):5274-5279
Two new classes of diphenylether inhibitors of p38alpha MAP kinase are described. Both chemical classes are based on a common diphenylether core that is identified by simulated fragment annealing as one of the most favored chemotypes within a prominent hydrophobic pocket of the p38alpha ATP-binding site. In the fully elaborated molecules, the diphenylether moiety acts as an anchor occupying the deep pocket, while polar extensions make specific interactions with either the adenine binding site or the phosphate binding site of ATP. The synthesis, crystallographic analysis, and biological activity of these p38alpha inhibitors are discussed. 相似文献
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Immunohistochemistry and Biosynthesis of N-Acetylaspartylglutamate in Spinal Sensory Ganglia 总被引:11,自引:10,他引:1
C. B. Cangro M. A. A. Namboodiri L. A. Sklar A. Corigliano-Murphy J. H. Neale 《Journal of neurochemistry》1987,49(5):1579-1588
N-Acetylaspartylglutamate (NAAG) is a nervous system-specific dipeptide which has been implicated in chemical neurotransmission. Antisera were prepared against NAAG in order to study its cellular distribution. When these antisera were applied to tissue sections of rat spinal sensory ganglia, NAAG-like immunoreactivity was detected within a subpopulation of relatively large neuronal cell bodies in cervical, lumbar, and thoracic ganglia. In order to confirm the presence of NAAG within these neurons, the dipeptide was extracted and purified from spinal ganglia using high-performance liquid chromatography and its composition confirmed by amino acid analysis. Further, the biosynthesis of NAAG was studied in vitro by following the incorporation of either [3H]glutamine or [3H]glutamate into the glutamate residue of the purified dipeptide. [3H]Aspartate was not incorporated efficiently into NAAG under these conditions, suggesting a precursor role for the large N-acetylaspartate pool. The incorporation of radiolabeled amino acids into newly synthesized NAAG by spinal sensory ganglia was not inhibited by incubation of the cells with anisomycin or cycloheximide at concentrations which significantly inhibited protein synthesis. These data suggest that NAAG is present in a subpopulation of primary afferent spinal neurons and that its biosynthesis is mediated by a dipeptide synthetase. 相似文献
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SpecP is an open-source Python module that performs Spectral Partitioning on Protein Contact Graphs. Protein Contact Graphs are
graph theory based representation of the protein structure, where each amino acid forms a ‘vertex’ and spatial contact of any two
amino acids is an ‘edge’ between them. Spectral partitioning is carried out in SpecP based on the second smallest spectral value
(eigen value) of the Protein Contact Graph. The eigen vector corresponding to the second smallest spectral value are partitioned
into two clusters based on the sign of the corresponding vector entry. Spectral Partitioning algorithm is repeatedly carried out until
the desired numbers of partitions are obtained. SpecP visualizes the spectrally partitioned clusters of protein structure along with
the Protein Contact Map and Protein Contact Graph which can be saved for later use. It also possesses an interactive mode
whereby the user has the ability to zoom, pan, resize and save these raster images in various image formats (.eps, .jpg, .png)
manually. SpecP is a stand-alone extensible tool useful for structural analysis of proteins. 相似文献
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M. A. A. Namboodiri Mini A. Namboodiri Joan L. Weller D. C. Klein 《Journal of neurochemistry》1979,32(1):31-33
pineal acetyl-CoA hydrolase is measurable at 4 days before birth. It increases rapidly to a maximum of 0.37 nmol/min/0.1 mg protein during the first week after birth, thereafter gradually decreasing and stabilizing at adult levels (0.27 nmol/min/0.1 mg protein) 3-4 weeks after birth. Unlike A/-acetyltransferase, the activity of acetyl-CoA hydrolase does not increase following treatment with isoproterenol, does not exhibit a circadian rhythm and is not inactivated on exposure of the animals to light at night. In addition, denervation of the pineal gland does not alter acetyl-CoA hydrolase activity. 相似文献
49.
Patrick M. Long Scott W. Tighe Heather E. Driscoll John R. Moffett Aryan M. A. Namboodiri Mariano S. Viapiano Sean E. Lawler Diane M. Jaworski 《PloS one》2013,8(11)
Cancer is associated with globally hypoacetylated chromatin and considerable attention has recently been focused on epigenetic therapies. N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate and ultimately acetyl-Coenzyme A for histone acetylation, are reduced in oligodendroglioma. The short chain triglyceride glyceryl triacetate (GTA), which increases histone acetylation and inhibits histone deacetylase expression, has been safely used for acetate supplementation in Canavan disease, a leukodystrophy due to ASPA mutation. We demonstrate that GTA induces cytostatic G0 growth arrest of oligodendroglioma-derived cells in vitro, without affecting normal cells. Sodium acetate, at doses comparable to that generated by complete GTA catalysis, but not glycerol also promoted growth arrest, whereas long chain triglycerides promoted cell growth. To begin to elucidate its mechanism of action, the effects of GTA on ASPA and acetyl-CoA synthetase protein levels and differentiation of established human oligodendroglioma cells (HOG and Hs683) and primary tumor-derived oligodendroglioma cells that exhibit some features of cancer stem cells (grade II OG33 and grade III OG35) relative to an oligodendrocyte progenitor line (Oli-Neu) were examined. The nuclear localization of ASPA and acetyl-CoA synthetase-1 in untreated cells was regulated during the cell cycle. GTA-mediated growth arrest was not associated with apoptosis or differentiation, but increased expression of acetylated proteins. Thus, GTA-mediated acetate supplementation may provide a safe, novel epigenetic therapy to reduce the growth of oligodendroglioma cells without affecting normal neural stem or oligodendrocyte progenitor cell proliferation or differentiation. 相似文献
50.
Narayanan Namboodiri 《Indian pacing and electrophysiology journal》2012,12(2):77-78