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排序方式: 共有796条查询结果,搜索用时 13 毫秒
161.
Hiromasa Oka Koichi Yonezawa Akio Kamikawa Kazuhiro Ikegai Norio Asai Shohei Shirakami Satoshi Miyamoto Toshihiro Watanabe Tetsuo Kiso Yukihiro Takemoto Seiji Tamura Takahiro Kuramochi 《Bioorganic & medicinal chemistry》2018,26(12):3716-3726
A new series of transient receptor potential vanilloid type 1 (TRPV1) antagonists were designed and synthesized from N-(3-hydroxyphenyl)-2-(piperidin-1-ylmethyl)biphenyl-4-carboxamide hydrochloride (8). SAR studies identified (R)-N-(1-methyl-2-oxo-1,2,3,4-tetrahydro-7-quinolyl)-2-[(2-methylpyrrolidin-1-yl)methyl]biphenyl-4-carboxamide hydrochloride (ASP8370, 7), as a compound with high aqueous solubility, satisfactory stability in human liver microsomes, and reduced CYP3A4 inhibition. ASP8370 was selected as a clinical development candidate with significant ameliorative effects on neuropathic pain. SAR studies also revealed the structural mechanisms underlying the switching between TRPV1 antagonism and agonism. 相似文献
162.
163.
LckBP1, a proline-rich protein expressed in haematopoietic lineage cells, directly associates with the SH3 domain of protein tyrosine kinase p56lck. 总被引:4,自引:0,他引:4
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The Lck tyrosine kinase molecule plays an essential role in T cell activation and T cell development. Using the expression cloning technique, we have isolated a gene that encodes a molecule, LckBP1, able to associate with murine Lck. Analysis of full-length LckBP1 cDNA indicates at least four potentially important segments: a four tandem 37 amino acid repeat motif with a potential helix-turn-helix DNA binding motif; a proline-rich region; a proline-glutamate repeat; and an SH3 domain. These four regions are very similar to the human haematopoietic-specific protein 1 (HS1). Deletion mutant analysis of LckBP1 revealed two proline-rich regions that permit association with Lck SH3. One region contains prolines conserved among HS1 and cortactin, and the other region contains a potential MAP kinase recognition site. In vivo association between Lck and LckBP1 was confirmed by immunoprecipitation of lysates from a pre-T cell line and adult thymocytes using antibodies specific for Lck and LckBP1. LckBP1 is tyrosine phosphorylated after T-cell receptor stimulation. The SH3 domain and the potential helix-turn-helix motif in LckBP1 suggest that this molecule may associate with various molecules and function as a DNA binding molecule. The data also suggest that LckBP1 mediates intracellular signalling through Lck in T cells. 相似文献
164.
A 570-kb DNA Sequence of the Escherichia coli K-12 Genome Corresponding to the 28.0-40.1 min Region on the Linkage Map 总被引:1,自引:0,他引:1
Aiba Hiroji; Baba Tomoya; Hayashi Kouji; Inada Toshifumi; Isono Katumi; Itoh Takeshi; Kasai Hiroaki; Kashimoto Kaoru; Kimura Shigenobu; Kitakawa Madoka; Kitagawa Masanari; Makino Kozo; Miki Takeyoshi; Mizobuchi Kiyoshi; Mori Hirotada; Mori Tomoko; Motomura Kouji; Nakade Shinsuke; Nakamura Yoshikazu; Nashimoto Hiroko; Nishio Yoshitaka; Oshima Taku; Saito Noriko; Sampei Gen-ichi; Seki Yasushi; Sivasundaram Suharnan; Tagami Hideaki; Takeda Jun-ichi; Takemoto Keiko; Takeuchi Yasushi; Wada Chieko; Yamamoto Yoshihiro; Horiuchi Takashi 《DNA research》1996,3(6):363-377
The 569,750 base pair sequence corresponding to the 28.040.1min region on the genetic map of Escherichia coli K-12 (W3110)was determined. This region includes the replication terminusregion and contained at least 549 potential open reading frames.Among them, 160 (29%) were previously reported, 174 (32%) werehomologous to other known genes, 102 (18%) were identical orsimilar to hypothetical genes registered in databases, and theremaining 113 (21%) did not show a significant similarity toany other gene. Of interest was the finding of a large numberof genes and gene clusters in andnear the replication terminationregion which had been thought to be genetically silent. Thoseincludeda cluster of genes for fatty acid ß-oxidation,the third copy of the pot (spermidine/putrescine transport system)gene cluster, the second dpp (dipeptide transport system) operon,the second dsm (anaerobic dimethyl sulfoxide reductase) operon,a cluster of fim (fimbrial) genes anda DNA helicase-like genewith a high molecular weight. In addition, we found the dnaC-and dnaT-like genes in the cryptic prophage, Rac, anda numberof genes originated probably from plasmids. 相似文献
165.
Abstract Syringomycin E (SR-E) is low molecular weight bacterial lipodepsipeptide with antifungal properties. Owing to immunosuppressive activities of such compounds as cyclosporine, FK506 and rapamycin, we studied the effect of SR-E on proliferation of human blood lymphocytes in vitro. SR-E, by itself, had no effect but the mitogen-induced lymphocyte proliferation was significantly suppressed. The suppressive effect was more pronounced with pokeweed mitogen (PWM) as compared to phytohemagglutinin (PHA) or monoclonal antibody to CD3 (anti-CD3). Since these mitogens induce cellular immunity (T cell-dependent), SR-E may potentially be a novel immunosuppressive compound. 相似文献
166.
The R40H mutation in a late onset type of human ornithine transcarbamylase deficiency in male patients 总被引:2,自引:0,他引:2
Atsushi Nishiyori M. Yoshino Hirohisa Kato Toshinobu Matsuura Ryuuji Hoshide Ichiro Matsuda Tateo Kuno Sumio Miyazaki Shin-ichi Hirose Ryu-ichi Kuromaru Masataka Mori 《Human genetics》1997,99(2):171-176
Ornithine transcarbamylase (OTC) deficiency is an X-linked trait and is one of the most frequent of the inherited urea cycle
enzyme deficiencies. Most male patients with OTC deficiency develop a hyperammonemic crisis and die in the neonatal period
or in early infancy. In contrast to those patients, in some male patients the disease first becomes overt in adolescence or
during the reproductive age period. In the present report, we describe six such male patients who first developed clinical
signs at ages ranging from 6 to 58 years, all of whom came from a limited area of the northern part of Kyushu Island in southern
Japan. The mutation analysis disclosed a R40H mutation in exon 2 of the OTC gene in each of these patients. Transmission of
this mutant gene through paternal lineage as well as through maternal lineage was documented in one family. The levels of
mRNA of the mutant OTC gene expressed in transfected Cos 1 cells and in the liver tissue obtained by biopsy in one patient
were both similar to those of the wild-type gene. The activity of the mutant OTC was, however, decreased to a level of 28%
of the wild-type OTC, and the levels of the mutant OTC protein expressed in Cos 1 cells were decreased, as assessed by western
blot analysis. Apparent K
m values of the mutant enzyme for ornithine (1.1 mM) and carbamylophosphate (2.0 mM) were similar to those of the wild-type
enzyme. Both enzymes gave similar pH-dependency profiles, giving a maximal activity at pH 7.8–7.9. Activity of wild-type OTC
expressed in Cos 1 cells did not change after five cycles of freezing and thawing, whereas that of the mutant OTC decreased
to 17% by this treatment. These results suggest that deficiency is due to inactivation of the mutant OTC under certain conditions.
Received: 15 May 1996 相似文献
167.
Dynamic reorganization of microfilaments and microtubules is necessary for the expression of non-host resistance in barley coleoptile cells 总被引:17,自引:1,他引:16
Yuhko Kobayashi Issei Kobayashi Yasuro Funaki Shigeo Fujimoto Tsuyoshi Takemoto Hitoshi Kunoh 《The Plant journal : for cell and molecular biology》1997,11(3):525-537
To show the involvement of microfilaments and microtubules in non-host resistance of barley, partially dissected coleoptiles which had been inoculated with a non-pathogen, Erysiphe pisi, were treated with several actin and tubulin inhibitors. If the coleoptiles were not treated with any of the inhibitors, the non-pathogen always failed to penetrate the coleoptile cells. However, when coleoptiles were treated with actin or tubulin polymerization or depolymerization inhibitors, the non-pathogen was able to penetrate successfully and to form haustoria in coleoptile cells of a non-host plant, barley. Actin polymerization inhibitors, cytochalasins, were more effective in causing an increase in penetration efficiency of E. pisi than tubulin inhibitors. The effects of cytochalasins depended on the kind of cytochalasin; the strength of the actin depolymerizing activity correlated significantly with the efficiency of increasing the penetration of the non-pathogen. When both actin and tubulin inhibitors were added simultaneously, the polarization of defense-related responses, such as massive cytoplasmic aggregation, deposition of papillae and accumulation of autofluorescent compounds, at fungal penetration sites was suppressed. Actin inhibitors did not affect arrangement and stability of microtubules and vice versa, and a double treatment of coleoptile cells with both microfilament and microtubule inhibitors showed an additive effect in increasing the penetration efficiency of E. pisi. Furthermore, cytochalasin A treatment allowed other non-pathogens, Colletotrichum lagenarium and Alternaria alternata, to penetrate successfully into the non-host barley cells. These results strongly suggest that microfilaments and microtubules might play important roles in the expression of non-host resistance of barley. 相似文献
168.
The effects of the bacterial phytotoxin, syringomycin, on stomata were investigated using detached leaves of Xanthium strumarium and isolated epidermes of Vicia faba. Syringomycin is known to cause K+ efflux in fungal and higher plant cells. Doses of syringomycin as low as 0.3 unit per square centimeter (about 0.88 pmole per square centimeter) resulted in measurable stomatal closure when applied through the transpiration stream of detached leaves; higher doses produced larger reductions in stomatal conductance. Stomatal apertures of isolated epidermes were also reduced by low concentrations (3.2 units per milliliter; 10−8 molar) of syringomycin. The effects of syringomycin were similar to those of ABA. Both compounds closed stomata at a similar rate and at similar concentrations. In addition, neither compound significantly affected the relationship between photosynthesis and intercellular CO2 based on data taken after stomatal conductance had stabilized following the treatment. It is possible that syringomycin and ABA activate the same K+ export system in guard cells, and syringomycin may be a valuable tool for studying the molecular basis of ABA effects on guard cells. 相似文献
169.
Antihypertensive effect of tryptic hydrolysate of milk casein in spontaneously hypertensive rats 总被引:14,自引:0,他引:14
H Karaki K Doi S Sugano H Uchiwa R Sugai U Murakami S Takemoto 《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》1990,96(2):367-371
1. Repeated oral administrations of tryptic hydrolysate of bovine milk casein (CEI) showed antihypertensive effect in spontaneously hypertensive rats. 2. Single oral administration of CEI antagonized the pressor response to angiotensin I. 3. Bovine milk casein hydrolysate inhibited the angiotensin I-converting enzyme (ACE) activity. Three peptides with ACE-inhibiting activity were isolated from CEI. 4. It is suggested that ACE-inhibiting peptides in the tryptic hydrolysate milk casein are absorbed from the intestinal tract and produce an antihypertensive effect. 相似文献
170.