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排序方式: 共有161条查询结果,搜索用时 18 毫秒
21.
Uchiro H Shionozaki N Kobayakawa Y Nakagawa H Makino K 《Bioorganic & medicinal chemistry letters》2012,22(14):4765-4768
A novel convergent method for the synthesis of α-acyl-γ-hydroxylactams utilizing the aldol reaction of N-Boc-protected γ-methoxylactams was developed. As the first application of this method for the synthesis of biologically active natural products, the total synthesis of platelet aggregation inhibitors PI-090 and PI-091 were also investigated and successfully achieved. 相似文献
22.
Kawakami F Yabata T Ohta E Maekawa T Shimada N Suzuki M Maruyama H Ichikawa T Obata F 《PloS one》2012,7(1):e30834
Leucine-rich repeat kinase 2 (LRRK2), a large protein kinase containing multi-functional domains, has been identified as the causal molecule for autosomal-dominant Parkinson's disease (PD). In the present study, we demonstrated for the first time that (i) LRRK2 interacts with tau in a tubulin-dependent manner; (ii) LRRK2 directly phosphorylates tubulin-associated tau, but not free tau; (iii) LRRK2 phosphorylates tau at Thr181 as one of the target sites; and (iv) The PD-associated LRRK2 mutations, G2019S and I2020T, elevated the degree of tau-phosphorylation. These results provide direct proof that tau is a physiological substrate for LRRK2. Furthermore, we revealed that LRRK2-mediated phosphorylation of tau reduces its tubulin-binding ability. Our results suggest that LRRK2 plays an important role as a physiological regulator for phosphorylation-mediated dissociation of tau from microtubules, which is an integral aspect of microtubule dynamics essential for neurite outgrowth and axonal transport. 相似文献
23.
T Kobayakawa S Shinbo H Ishiyama K Masuda 《Japanese journal of medical science & biology》1976,29(6):351-357
Parasiticidal activity of normal peritoneal exudate cells on microfilariae of Dirofilaria immitis in diffusion chambers implanted into normal guinea pigs was evoked by intraperitoneal passive transfer of anti-D. immitis serum. The immune serum was fractionated into supernatant and sediment by ammonium sulfate precipitation. The parasiticidal effect was reproduced with the supernatant and, to a less extent, with the sediment. Anti-D. immitis serum from the animals sensitized 5 days before was also effective in this respect. From these results it can be concluded that the factor responsible for the phenomenon is some other factor(s) than the antibody. In addition, the in vitro cytotoxicity test demonstrated an enhanced Mf-killing activity of sensitized peritoneal exudate cells by adding with anti-D. immitis serum. 相似文献
24.
Misato Suzuki Fumiya Nakamura Emi Taguchi Maho Nakata Fumi Wada Momoka Takihi Tomoyo Inoue Shinji Ohta Hiroyuki Kawachi 《Molecular and cellular biochemistry》2018,438(1-2):35-45
Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr kinase family, and is associated with different types of cancer and neurodegenerative diseases. Vanillin is a natural compound, a primary component of the extract of the vanilla bean which possesses varieties of pharmacological features including anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor. Here, we have investigated the binding mechanism and affinity of vanillin to the CAMKIV which is being considered as a potential drug target for cancer and neurodegenerative diseases. We found that vanillin binds strongly to the active site cavity of CAMKIV and stabilized by a large number of non-covalent interactions. We explored the utility of vanillin as anti-cancer agent and found that it inhibits the proliferation of human hepatocyte carcinoma (HepG2) and neuroblastoma (SH-SY5Y) cells in a dose-dependent manner. Furthermore, vanillin treatment resulted into the significant reduction in the mitochondrial membrane depolarization and ROS production that eventually leads to apoptosis in HepG2 and SH-SY5Y cancer cells. These findings may offer a novel therapeutic approach by targeting the CAMKIV using natural product and its derivative with a minimal side effect. 相似文献
25.
Takuya Kobayakawa Nami Ohashi Yuki Hirota Kohei Takahashi Yuko Yamada Tetsuo Narumi Kazuhisa Yoshimura Shuzo Matsushita Shigeyoshi Harada Hirokazu Tamamura 《Bioorganic & medicinal chemistry》2018,26(21):5664-5671
CD4 mimics such as YIR-821 and its derivatives are small molecules which inhibit the interaction between the Phe43 cavity of HIV-1 gp120 with host CD4, an interaction that is involved in the entry of HIV to cells. Known CD4 mimics generally possess three structural features, an aromatic ring, an oxalamide linker and a piperidine moiety. We have shown previously that introduction of a cyclohexyl group and a guanidine group into the piperidine moiety and a fluorine atom at the meta-position of the aromatic ring leads to a significant increase in the anti-HIV activity. In the current study, the effects of conformational flexibility were investigated by introduction of an indole-type group in the junction between the oxalamide linker and the aromatic moiety or by replacement of the oxalamide linker with a glycine linker. This led to the development of compounds with high anti-HIV activity, showing the importance of the junction region for the expression of high anti-HIV activity. The present data are expected to be useful in the future design of novel CD4 mimic molecules. 相似文献
26.
Kazutaka Miyamoto Mizuha Akiyama Fumiya Tamura Mari Isomi Hiroyuki Yamakawa Taketaro Sadahiro Naoto Muraoka Hidenori Kojima Sho Haginiwa Shota Kurotsu Hidenori Tani Li Wang Li Qian Makoto Inoue Yoshinori Ide Junko Kurokawa Tsunehisa Yamamoto Tomohisa Seki Masaki Ieda 《Cell Stem Cell》2018,22(1):91-103.e5
27.
Toshitsugu Kawata Chiyoko Tokimasa Tadashi Fujita Masato Kaku Keisuke Tsutsui Shinya Kohno Akira Matsuki Kaoru Tenjo Junji Ohtani Masahide Motokawa Takashi Kobayakawa Mao Shigekawa Kazuo Tanne 《Experimental Animals》2002,51(5):521-524
The time-dependent effects of daily dosing of IGF-I (1.21 mg/g) on the linear growth of the femur were investigated in mice. The femoral length and volume and the number of osteoclasts were significantly greater after IGF-I injection as compared to the non-injected control, suggesting that the IGF-I imbalance might cause a quick turnover cycle of the bone resulting in the altered femoral modeling. 相似文献
28.
Toshio Yamaguchi Fumiya Kurosaki Dae-Yeon Suh Ushio Sankawa Mizue Nishioka Takumi Akiyama Masaaki Shibuya Yutaka Ebizuka 《FEBS letters》1999,460(3)
Chalcone synthase (CHS) and stilbene synthase (STS) are related plant polyketide synthases belonging to the CHS superfamily. CHS and STS catalyze common condensation reactions of p-coumaroyl-CoA and three C2-units from malonyl-CoA but different cyclization reactions to produce naringenin chalcone and resveratrol, respectively. Using purified Pueraria lobata CHS and Arachis hypogaea STS overexpressed in Escherichia coli, bisnoryangonin (BNY, the derailed lactone after two condensations) and p-coumaroyltriacetic acid lactone (the derailed lactone after three condensations) were detected from the reaction products. More importantly, we found a cross-reaction between CHS and STS, i.e. resveratrol production by CHS (2.7–4.2% of naringenin) and naringenin production by STS (1.4–2.3% of resveratrol), possibly due to the conformational flexibility of their active sites. 相似文献
29.
Exclusion of assembled MreB by anionic phospholipids at cell poles confers cell polarity for bidirectional growth
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Takuma Kawazura Kanon Matsumoto Koki Kojima Fumiya Kato Tomomi Kanai Hironori Niki Daisuke Shiomi 《Molecular microbiology》2017,104(3):472-486
Cell polarity determines the direction of cell growth in bacteria. MreB actin spatially regulates peptidoglycan synthesis to enable cells to elongate bidirectionally. MreB densely localizes in the cylindrical part of the rod cell and not in polar regions in Escherichia coli. When treated with A22, which inhibits MreB polymerization, rod‐shaped cells became round and MreB was diffusely distributed throughout the cytoplasmic membrane. A22 removal resulted in restoration of the rod shape. Initially, diffuse MreB started to re‐assemble, and MreB‐free zones were subsequently observed in the cytoplasmic membrane. These MreB‐free zones finally became cell poles, allowing the cells to elongate bidirectionally. When MreB was artificially located at the cell poles, an additional pole was created, indicating that artificial localization of MreB at the cell pole induced local peptidoglycan synthesis. It was found that the anionic phospholipids (aPLs), phosphatidylglycerol and cardiolipin, which were enriched in cell poles preferentially interact with monomeric MreB compared with assembled MreB in vitro. MreB tended to localize to cell poles in cells lacking both aPLs, resulting in production of Y‐shaped cells. Their findings indicated that aPLs exclude assembled MreB from cell poles to establish cell polarity, thereby allowing cells to elongate in a particular direction. 相似文献
30.
Toshio Takahashi Osamu Koizumi Eisuke Hayakawa Sumiko Minobe Rinako Suetsugu Yoshitaka Kobayakawa Thomas C. G. Bosch Charles N. David Toshitaka Fujisawa 《Development genes and evolution》2009,219(3):119-129
From an evolutionary point of view, Hydra has one of the most primitive nervous systems among metazoans. Two different groups of peptides that affect neuron differentiation
were identified in a systematic screening of peptide signaling molecules in Hydra. Within the first group of peptides, a neuropeptide, Hym-355, was previously shown to positively regulate neuron differentiation.
The second group of peptides encompasses the PW family of peptides that negatively regulate neuron differentiation. In this
study, we identified the gene encoding PW peptide preprohormone. Moreover, we made the antibody that specifically recognizes
LPW. In situ hybridization and immunohistochemical analyses showed that the PW peptides and the gene encoding them were expressed
in ectodermal epithelial cells throughout the body except for the basal disk. The PW peptides are produced by epithelial cells
and are therefore termed “epitheliopeptides.” Together with Hym-355, the PW family peptides mediate communication between
neurons and epithelial cells and thereby maintain a specific density of neurons in Hydra.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Toshio Takahashi, Osamu Koizumi equally contributed to this study. 相似文献