排序方式: 共有23条查询结果,搜索用时 15 毫秒
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Ojas A. Namjoshi Zhi-jian Wang Sundari K. Rallapalli Edward Merle Johnson Yun-Teng Johnson Hanna Ng Joachim Ramerstorfer Zdravko Varagic Werner Sieghart Samarpan Majumder Bryan L. Roth James K. Rowlett James M. Cook 《Bioorganic & medicinal chemistry》2013,21(1):93-101
Selective modulation of specific benzodiazepine receptor (BzR) gamma amino butyric acid-A (GABAA) receptor ion channels has been identified as an important method for separating out the variety of pharmacological effects elicited by BzR-related drugs. Importantly, it has been demonstrated that both α2β(2/3)γ2 (α2BzR) and α3BzR (and/or α2/α3) BzR subtype selective ligands exhibit anxiolytic effects with little or no sedation. Previously we have identified several such ligands; however, three of our parent ligands exhibited significant metabolic liability in rodents in the form of a labile ester group. Here eight analogs are reported which were designed to circumvent this liability by utilizing a rational replacement of the ester moiety based on medicinal chemistry precedents. In a metabolic stability study using human liver microsomes, four compounds were found to undergo slower metabolic transformation, as compared to their corresponding ester analogs. These compounds were also evaluated in in vitro efficacy assays. Additionally, bioisostere 11 was evaluated in a rodent model of anxiety. It exhibited anxiolytic activity at doses of 10 and 100 mg/kg and was devoid of sedative properties. 相似文献
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Ectopic expression of snapdragon transcription factors facilitates the identification of genes encoding enzymes of anthocyanin decoration in tomato
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SERRATE: a new player on the plant microRNA scene 总被引:7,自引:0,他引:7
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Efficient chondrogenic differentiation of mesenchymal cells in micromass culture by retroviral gene transfer of BMP-2 总被引:11,自引:0,他引:11
A.L. Carlberg · B. Pucci · R. Rallapalli · R.S. Tuan · D.J. Hall 《Differentiation; research in biological diversity》2001,67(4-5):128-138
The multipotential murine embryonic C3H10T1/2 mesenchymal cell line is able to undergo chondrogenesis in vitro, in a high density micromass environment, following treatment with soluble human bone morphogenetic protein-2 (BMP-2). To enhance this process, the human BMP-2 cDNA was cloned into a retroviral expression vector and a high titer, infectious retrovirus (replication defective) was generated. Infection of C3HIOT1/2 cells with this retroviral construct resulted in an infection efficiency of 90-95% and was highly effective in converting cells in micromass culture to a chondrocyte phenotype, as assessed by positive Alcian blue staining for extracellular matrix proteoglycans, increased sulfate incorporation, increased expression of the cartilage marker genes collagen type II and aggrecan, and decreased expression of collagen type I. Interestingly, BMP-2 expression in the micromass cultures also induced the expression of the cell cycle inhibitory protein/differentiation factor p21/WAF1, suggesting its functional involvement in chondrogenesis. The chondrogenic effect of retrovirally expressed BMP-2 in these high-density cultures was limited to the infected cells, since uninfected cells did not chondrify when co-cultured as a nonoverlapping micromass adjacent to BMP-2 expressing cells. These data indicate that retrovirally expressed BMP-2 is highly effective at inducing a chondrocyte phenotype in a multipotential mesenchymal cell line in vitro, and its action is restricted to the infected cell population. These findings should provide a framework for the optimization of chondrogenesis in culture using mesenchymal stem cells and retroviral gene transfer. 相似文献
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Lysyl tRNA synthetases facilitate amino acylation and play a crucial role in the essential cellular process of translation. They are grouped into two distinct classes (class I and class II). Class I lysyl tRNA synthetase is considered as a drug target for syphilis caused by Treponema pallidum. Comparative genome analysis shows the absence of its sequence homolog in eukaryotes. The structure of class I lysyl tRNA synthetase from Treponema pallidum is unknown and the difficulties in the in vitro culturing of Treponema makes it non-trivial. We used the structural template of class I lysyl tRNA synthetase from the archaea Pyrococcus horikoshii for modeling the Treponema pallidum lysyl tRNA synthetase structure. Thus, we propose the usefulness of the modeled class I lysyl tRNA synthetase for the design of suitable inhibitors towards the treatment of syphilis. 相似文献