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951.
Toru Nemoto Naoshi Yamamoto Naohisa Wada Yukimasa Harada Miyuki Tomatsu Marina Ishihara Shigeto Hirayama Takashi Iwai Hideaki Fujii Hiroshi Nagase 《Bioorganic & medicinal chemistry letters》2013,23(1):268-272
We have previously reported the essential structure of the opioid κ receptor agonist nalfurafine hydrochloride (TRK-820) for binding to the κ receptor. In the course of this study, we focused on the effect of the substituent at 17-N in nalfurafine on the binding affinity for the κ receptor. The exchange of the 17-N substituent in nalfurafine from cyclopropylmethyl to fluoro-substituted alkyl groups, which are strong electron withdrawing substituents, almost completely diminished the binding affinities for the μ and δ opioid receptors, but the binding affinity for the κ receptor was still maintained. As a result, nalfurafine derivatives with 17-fluoro-substituted alkyl groups showed higher selectivities for the κ receptor than did nalfurafine itself. With regard to the κ agonistic activities, the conversion of the 17-N substituent in nalfurafine from cyclopropylmethyl to fluoro-substituted alkyl groups led to the gradual decrease of the agonistic activities in the order corresponding to their binding affinities for the κ receptor. In contrast, the derivative with the bulky 17-isobutyl group showed lower affinity and agonistic activity for the κ receptor than the derivatives with the smaller functional groups. This research suggested that both the electronic property and the steric characteristics of the 17-N substituent would have a great influence on the binding property for the κ receptor. 相似文献
952.
Toru Nemoto Yoshihiro Ida Yusuke Iihara Ryo Nakajima Shigeto Hirayama Takashi Iwai Hideaki Fujii Hiroshi Nagase 《Bioorganic & medicinal chemistry》2013,21(24):7628-7647
We investigated the structure–activity relationship of KNT-127 (opioid δ agonist) derivatives with various 17-substituents which are different in length and size. The 17-substituent in KNT-127 derivatives exerted a great influence on the affinity and agonistic activity for the δ receptor. While the compounds with electron-donating 17-substituents showed higher affinities for the δ receptor than those with electron-withdrawing groups, KNT-127 derivatives with 17-fluoroalkyl groups (the high electron-withdrawing groups) showed high selectivities for the δ receptor among evaluated compounds. In addition, the basicity of nitrogen as well as the structure of the 17-N substituent such as the length and configuration at an asymmetric carbon atom contributed to agonist properties for the δ receptor. Thus, the analog with a 17-(3-ethoxypropyl) group showed the best selectively and potent agonistic activity for the δ receptor among KNT-127 derivatives. These findings should be useful for designing novel δ selective agonists. 相似文献
953.
Yoshifuji Natsuko Kumagai Tomo’omi Ichie Tomoaki Kume Tomonori Tateishi Makiko Inoue Yuta Yoneyama Aogu Nakashizuka Tohru 《Journal of plant research》2020,133(2):175-191
Journal of Plant Research - The physiological response of trees to drought is crucial for understanding the risk of mortality and its feedbacks to climate under the increase in droughts due to... 相似文献
954.
Kayo Imamura Takanori Matsuura Atsushi Nakagawa Shinichi Kitamura Masami Kusunoki Takeshi Takaha Hideaki Unno 《Protein science : a publication of the Protein Society》2020,29(10):2085-2100
Starch produced by plants is a stored form of energy and is an important dietary source of calories for humans and domestic animals. Disproportionating enzyme (D‐enzyme) catalyzes intramolecular and intermolecular transglycosylation reactions of α‐1, 4‐glucan. D‐enzyme is essential in starch metabolism in the potato. We present the crystal structures of potato D‐enzyme, including two different types of complex structures: a primary Michaelis complex (substrate binding mode) for 26‐meric cycloamylose (CA26) and a covalent intermediate for acarbose. Our study revealed that the acarbose and CA26 reactions catalyzed by potato D‐enzyme involve the formation of a covalent intermediate with the donor substrate. HPAEC of reaction substrates and products revealed the activity of the potato D‐enzyme on acarbose and CA26 as donor substrates. The structural and chromatography analyses provide insight into the mechanism of the coupling reaction of CA and glucose catalyzed by the potato D‐enzyme. The enzymatic reaction mechanism does not involve residual hydrolysis. This could be particularly useful in preventing unnecessary starch degradation leading to reduced crop productivity. Optimization of this mechanism would be important for improvements of starch storage and productivity in crops. 相似文献
955.
956.
Ohno H Nakatsu Y Sakoda H Kushiyama A Ono H Fujishiro M Otani Y Okubo H Yoneda M Fukushima T Tsuchiya Y Kamata H Nishimura F Kurihara H Katagiri H Oka Y Asano T 《American journal of physiology. Cell physiology》2011,300(5):C1047-C1054
Glucose transporter 1 (GLUT1) is widely distributed throughout various tissues and contributes to insulin-independent basal glucose uptake. Using a split-ubiquitin membrane yeast two-hybrid system, we newly identified 4F2 heavy chain (4F2hc) as a membrane protein interacting with GLUT1. Though 4F2hc reportedly forms heterodimeric complexes between amino acid transporters, such as LAT1 and LAT2, and regulates amino acid uptake, we investigated the effects of 4F2hc on GLUT1 expression and the associated glucose uptake. First, FLAG-tagged 4F2hc and hemagglutinin-tagged GLUT1 were overexpressed in human embryonic kidney 293 cells and their association was confirmed by coimmunoprecipitation. The green fluorescent protein-tagged 4F2hc and DsRed-tagged GLUT1 showed significant, but incomplete, colocalization at the plasma membrane. In addition, an endogenous association between GLUT1 and 4F2hc was demonstrated using mouse brain tissue and HeLa cells. Interestingly, overexpression of 4F2hc increased the amount of GLUT1 protein in HeLa and HepG2 cells with increased glucose uptake. In contrast, small interfering RNA (siRNA)-mediated 4F2hc gene suppression markedly reduced GLUT1 protein in both cell types, with reduced glucose uptake. While GLUT1 mRNA levels were not affected by overexpression or gene silencing of 4F2hc, GLUT1 degradation after the addition of cycloheximide was significantly suppressed by 4F2hc overexpression and increased by 4F2hc siRNA treatment. Taken together, these observations indicate that 4F2hc is likely to be involved in GLUT1 stabilization and to contribute to the regulation of not only amino acid but also glucose metabolism. 相似文献
957.
Kume S 《Neurochemical research》2011,36(7):1280-1285
Nearly 20 years ago Professor Katsuhiko Mikoshiba led me to an exciting world of IP3-Ca2+ signaling, we embarked on the role of IP3-Ca2+ signaling on fertilization, early cell cycle progression, and body axis formation. I was fully enchanted by the world of
basic science, particularly developmental biology. It is a great pleasure to contribute a paper to this special issue of Neurochemical
Research honoring Professor Katsuhiko Mikoshiba. Many of the former lab members are now working in a wide range of fields,
both inside or outside the fields of Neurochemical research. I am one of those who are working in a different field. Therefore,
it seems fitting here to first write about our former work with IP3 receptor, and then introduce our recent works. 相似文献
958.
Yuichiro Kogura James E. Seeb Noriko Azuma Hideaki Kudo Syuiti Abe Masahide Kaeriyama 《Environmental Biology of Fishes》2011,92(4):539-550
Lacustrine sockeye salmon (Oncorhynchus nerka) are listed as an endangered species in Japan despite little genetic information on their population structure. In order
to clarify the genetic diversity and structure of Japanese populations for evaluating on the bottleneck effect and an endangered
species, we analyzed the ND5 region of mitochondrial DNA (mtDNA) and 45 single nucleotide polymorphisms (SNPs) in 640 lacustrine sockeye salmon in Japan
and 80 anadromous sockeye salmon in Iliamna Lake of Alaska. The genetic diversity of the Japanese population in both mtDNA
and SNPs was significantly less than that of the Iliamna Lake population. Moreover, all Japanese populations had SNP loci
deviating from the HWE. In spite of low genetic diversity, the SNP analyses resulted that the Japanese population was significantly
divided into three groups. These suggest that Japanese sockeye salmon populations should be protected as an endangered species
and genetically disturbed by the hatchery program and transplantations. 相似文献
959.
Nishioka Y Oyagi A Tsuruma K Shimazawa M Ishibashi T Hara H 《BioFactors (Oxford, England)》2011,37(1):25-30
Astaxanthin is a red carotenoid pigment and is widely found in living organisms. Astaxanthin has a potent antioxidative ability and has been reported as having various biological effects on the central nerve system, such as a protective effect against ischemia/reperfusion injury and improvement in cognitive function. In this study, to investigate the effects of astaxanthin on anxiety and depression, we performed some behavioral trials including the elevated plus maze test, hole-board test, forced swim test, and tail suspension test. Astaxanthin (100 and 300 mg/kg/day for 10 days, p.o.) significantly increased the time spent in open arms in the elevated plus maze test and increased the head-dipping count and duration in the hole-board test. On the other hand, astaxanthin (10, 100, 300, and 500 mg/kg/day for 10 days, p.o.) did not change the immobility time in the forced swim test or the tail suspension test. In conclusion, in mice, astaxanthin exerted anxiolytic-like effects, but not antidepressant-like effects. 相似文献
960.
The structures and biosynthesis of lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, have been studied extensively in cultured bacteria such as Escherichia coli. In contrast, little is known about the structures and biosynthesis of the LPS of unculturable bacteria, including insect symbionts, many of which are Gram-negative bacteria. A brown-winged green bug, Plautia stali, is known to harbor a single species of gamma-proteobacterium in the posterior mid-gut caeca. To characterize the features of its LPS, we analyzed the genome sequence of the symbiont, and identified the putative genes involved in LPS synthesis. Genes involved in the synthesis of lipid A and the core oligosaccharide were found in the genome, but waaL, which encodes the O-antigen ligase, was not. Furthermore, we characterized the LPS of this symbiont using SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Toll-like receptor 4 (TLR4) stimulation assays. Consistent with the genomic analysis, the SDS-PAGE analysis suggested that the symbiont had rough-type LPS, which lacked the O-antigen. The TLR4 stimulation assay demonstrated that LPS purified from the symbionts activated NF-κB-dependent reporter expression, indicating the existence of a bioactive lipid A portion in the LPS. These results suggest that the P. stali symbiont produces rough-type LPS. 相似文献