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排序方式: 共有492条查询结果,搜索用时 15 毫秒
421.
Takumi Watanabe Yoji Umezawa Yoshikazu Takahashi Yuzuru Akamatsu 《Bioorganic & medicinal chemistry letters》2010,20(19):5807-5810
Pyrrole- and 1,2,3-triazole-based 2,3-oxidosqualene cyclase (OSC) inhibitors 3 and 4 were discovered by conducting a virtual screening, a docking study based on the crystallographic structure of OSC, and biological assays. The hit rate of the assays was increased by establishing appropriate substructural filters in the virtual screening stage. Amide derivatives of 8 and 12 preserved the inhibitory activity of parent compound 3, which provided a reasonable starting point for further structure–activity-relationship (SAR) studies on related compounds. 相似文献
422.
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424.
Li L Tatake RJ Natarajan K Taba Y Garin G Tai C Leung E Surapisitchat J Yoshizumi M Yan C Abe J Berk BC 《Biochemical and biophysical research communications》2008,370(1):159-163
Steady laminar blood flow protects vessels from atherosclerosis. We showed that flow decreased tumor necrosis factor-α (TNF)-mediated VCAM1 expression in endothelial cells (EC) by inhibiting JNK. Here, we determined the relative roles of MEK1, MEK5 and their downstream kinases ERK1/2 and BMK1 (ERK5) in flow-mediated inhibition of JNK activation. Steady laminar flow (shear stress = 12 dyn/cm2) increased BMK1 and ERK1/2 activity in EC. Pre-exposing EC for 10 min to flow inhibited TNF activation of JNK by 58%. A key role for BMK1, but not ERK1/2 was shown. (1) Incubation of EC with PD184352, at concentrations that blocked ERK1/2, but not BMK1, had no effect on flow inhibition of TNF-mediated JNK activation. (2) BIX02188, a MEK5-selective inhibitor, completely reversed the inhibitory effects of flow. These findings indicate that flow inhibits TNF-mediated signaling events in EC by a mechanism dependent on activation of MEK5-BMK1, but not MEK1-ERK1/2. These results support a key role for the MEK5-BMK1 signaling pathway in the atheroprotective effects of blood flow. 相似文献
425.
Site-selective and hydrolytic two-strand scission of double-stranded DNA using Ce(IV)/EDTA and pseudo-complementary PNA
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Yoji Yamamoto Akihiko Uehara Takafumi Tomita Makoto Komiyama 《Nucleic acids research》2004,32(19):e153
By combining Ce(IV)/EDTA with two pseudo-complementary peptide nucleic acids (pcPNAs), both strands in double-stranded DNA were site-selectively hydrolyzed at the target site. Either plasmid DNA (4361 bp) or its linearized form was used as the substrate. When two pcPNAs invaded into the double-stranded DNA, only the designated portion in each of the two strands was free from Watson–Crick base pairing with the counterpart DNA or the pcPNA. Upon the treatment of this invasion complex with Ce(IV)/EDTA at 37°C and pH 7.0, both of these single-stranded portions were selectively hydrolyzed at the designated site, resulting in the site-selective two-strand scission of the double-stranded DNA. Furthermore, the hydrolytic scission products were successfully connected with foreign double-stranded DNA by using ligase. The potential of these artificial systems for manipulation of huge DNA has been indicated. 相似文献
426.
Nolz JC Gomez TS Zhu P Li S Medeiros RB Shimizu Y Burkhardt JK Freedman BD Billadeau DD 《Current biology : CB》2006,16(1):24-34
BACKGROUND: The engagement of the T cell receptor results in actin cytoskeletal reorganization at the immune synapse (IS) and the triggering of biochemical signaling cascades leading to gene regulation and, ultimately, cellular activation. Recent studies have identified the WAVE family of proteins as critical mediators of Rac1-induced actin reorganization in other cell types. However, whether these proteins participate in actin reorganization at the IS or signaling pathways in T cells has not been investigated. RESULTS: By using a combination of biochemical, genetic, and cell biology approaches, we provide evidence that WAVE2 is recruited to the IS, is biochemically modified, and is required for actin reorganization and beta-integrin-mediated adhesion after TCR crosslinking. Moreover, we show that WAVE2 regulates calcium entry at a point distal to PLCgamma1 activation and IP(3)-mediated store release. CONCLUSIONS: These data reveal a role for WAVE2 in regulating multiple pathways leading to T cell activation. In particular, this work shows that WAVE2 is a key component of the actin regulatory machinery in T cells and that it also participates in linking intracellular calcium store depletion to calcium release-activated calcium (CRAC) channel activation. 相似文献
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428.
Masahiro Asano Satoshi Kubota Tohru Nakanishi Takashi Nishida Tomoichiro Yamaai Gen Yosimichi Kazumi Ohyama Tomosada Sugimoto Yoji Murayama Masaharu Takigawa 《Cell communication and signaling : CCS》2005,3(1):1-11
Background
CCN2/CTGF is known to be involved in tooth germ development and periodontal tissue remodeling, as well as in mesenchymal tissue development and regeneration. In this present study, we investigated the roles of CCN2/CTGF in the proliferation and differentiation of periodontal ligament cells (murine periodontal ligament-derived cell line: MPL) in vitro.Results
In cell cultures of MPL, the mRNA expression of the CCN2/CTGF gene was stronger in sparse cultures than in confluent ones and was significantly enhanced by TGF-β. The addition of recombinant CCN2/CTGF (rCCN2) to MPL cultures stimulated DNA synthesis and cell growth in a dose-dependent manner. Moreover, rCCN2 addition also enhanced the mRNA expression of alkaline phosphatase (ALPase), type I collagen, and periostin, the latter of which is considered to be a specific marker of the periosteum and periodontium; whereas it showed little effect on the mRNA expression of typical osteoblastic markers, e.g., osteopontin and osteocalcin. Finally, rCCN2/CTGF also stimulated ALPase activity and collagen synthesis.Conclusion
These results taken together suggest important roles of CCN2/CTGF in the development and regeneration of periodontal tissue including the periodontal ligament. 相似文献429.
Momose I Umezawa Y Hirosawa S Iijima M Iinuma H Ikeda D 《Bioscience, biotechnology, and biochemistry》2005,69(9):1733-1742
Tyropeptin A, a potent proteasome inhibitor, was isolated from the culture broth of Kitasatospora sp. MK993-dF2. We synthesized the derivatives of tyropeptin A to enhance its inhibitory potency. Among the synthesized derivatives, the most potent compound, TP-104, exhibited a 20-fold inhibitory potency enhancement for chymotrypsin-like activity of 20S proteasome compared to tyropeptin A. Additionally, TP-110 specifically inhibited the chymotrypsin-like activity, but did not inhibit the post-glutamyl-peptide hydrolyzing (PGPH) and the trypsin-like activities of 20S proteasome. In vitro TP-110 strongly inhibited the growth of various cell lines. 相似文献
430.
Serrawettin W1 produced by Serratia marcescens is a surface active exolipid having various functions supporting behaviors of bacteria on surface environments. Through the genetic analyses of serrawettin-less mutants of S. marcescens 274, the swrW gene encoding putative serrawettin W1 synthetase was identified. Homology analysis of the putative SwrW demonstrated the presence of condensation, adenylation, thiolation, and thioesterase domains which are characteristic for nonribosomal peptide synthetase (NRPS). NRPSs have been known as multi-modular enzymes. Linear alignment of these modules specifying respective amino acids will enable peptide bond formation resulting in a specific amino acid sequence. Putative SwrW was uni-modular NRPS specifying only L-serine. Possible steps in this simple unimodular NRPS for biosynthesis of serrawettin W1 [ cyclo-(D-3-hydroxydecanoyl-L-seryl) (2) ] were predicted by referring to the ingenious enzymatic activity of gramicidin S synthetase (multi-modular NRPS) of Brevibacillus brevis. 相似文献