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81.
Watanabe Y Kitazawa S Fujii H Nemoto T Hirayama S Nagase H 《Bioorganic & medicinal chemistry letters》2012,22(8):2689-2692
A novel opioid ligand possessing a stable and cyclic imine 16 and its derivatives with an azabicyclo[2.2.2]octane skeleton were synthesized. The imine 16 showed higher affinity for the μ receptor than compound 21 with an oxabicyclo[2.2.2]octane skeleton. Azabicyclo[2.2.2]octane derivative 18d with a cyclopropylmethyl group on the 8-nitrogen showed the highest affinity for the μ receptor among the synthesized derivatives. 相似文献
82.
Haidong Tan Yueguang Li Ling Chen Takayuki Kudoh Tomonari Kasai Masaharu Seno 《Molecular Biology》2012,46(1):142-148
Green fluorescent protein (GFPuv) has been widely used as a reporter fused to individual targeting sequences. However, its
state in liquid and its effect on other proteins are still unclear. The conformational polymorphisms of glutathione-S-transferase-green
fluorescent protein (GST-GFPuv), GFPuv and GST were analyzed by native polyacrylamide gel, indicating that GST was in many
different states while GFPuv and GST-GFPuv were only in four and two slightly different states. Four different circular dichroism
spectra were obtained from the GFPuv polymorphisms. The single molecular behavior of GST-GFPuv and GFPuv was also characterized
by MALDI-TOF MS. Thus, we demonstrated that: (1) there might be four different structural polymorphisms for the native GFPuv;
(2) GFPuv could reduce its partner’s polymorphism as a fusion protein. Although GFPuv had many merits as a reporter, its unreliability
was found in the study. 相似文献
83.
Hideaki Fujii Satomi Imaide Shigeto Hirayama Toru Nemoto Hiroaki Gouda Shuichi Hirono Hiroshi Nagase 《Bioorganic & medicinal chemistry letters》2012,22(24):7711-7714
To clarify the essential structures of an opioid κ receptor selective agonist, nalfurafine, for binding to the κ receptor, we designed and synthesized the decahydro(iminoethano)phenanthrene derivatives with an oxygen functionality at the 3-position. The introduction of a hydroxy group to the derivatives increased the affinity and selectivity to the κ receptor regardless of the configuration at the 3-position. However, their affinities were lower than those of nalfurafine with the phenolic hydroxy group. The results suggested that the acidity of the hydroxy group would play an important role in the interaction with the opioid receptor. The low affinities of the 3-keto derivatives indicated that the 3-hydroxy group may participate in the hydrogen bonding with the receptor site not as a hydrogen acceptor but as a hydrogen donor. This is the first experimental evidence for a role as a hydrogen donor for the 3-hydroxy group in morphinans. Furthermore, the κ selectivities in these derivatives with the 6α-amide side chain were affected by the the 3-hydroxy group. The obtained structure–activity relationship information is expected to be useful for the design of more selective ligands for the κ receptor. 相似文献
84.
85.
Yoshihiro Ida Ayaka Matsubara Toru Nemoto Manabu Saito Shigeto Hirayama Hideaki Fujii Hiroshi Nagase 《Bioorganic & medicinal chemistry》2012,20(19):5810-5831
We have reported previously the novel δ opioid agonist KNT-127 which showed high affinity and selectivity for the δ receptor. Moreover, the analgesic effect of subcutaneously administered KNT-127 was more potent than that of a prototypical δ agonist (?)-TAN-67 in the acetic acid writhing test. This study of the structure–activity relationship of KNT-127 derivatives focused on the introduction of substituents onto the 5′-, 6′-, 7′- or 8′-position of the quinoline ring and revealed that many derivatives with 5′- or 8′-substituents showed high affinities and selectivities for the δ receptor. Especially, SYK-153 with an 8′-OH group showed the highest affinity and the most balanced and highest selectivity for the δ receptor among the synthesized compounds. 相似文献
86.
Nojima T Murayama S Yoshida M Motojima F 《The Journal of biological chemistry》2008,283(26):18385-18392
A double-heptamer ring chaperonin GroEL binds denatured substrate protein, ATP, and GroES to the same heptamer ring and encapsulates substrate into the central cavity underneath GroES where productive folding occurs. GroES is a disk-shaped heptamer, and each subunit has a GroEL-binding loop. The residues of the GroEL subunit responsible for GroES binding largely overlap those involved in substrate binding, and the mechanism by which GroES can replace the substrate when GroES binds to GroEL/substrate complex remains to be clarified. To address this question, we generated single polypeptide GroES by fusing seven subunits with various combinations of active and GroEL binding-defective subunits. Functional tests of the fused GroES variants indicated that four active GroES subunits were required for efficient formation of the stable GroEL/GroES complex and five subunits were required for the productive GroEL/substrate/GroES complex. An increase in the number of defective GroES subunits resulted in a slowing of encapsulation and folding. These results indicate the presence of an intermediate GroEL/substrate/GroES complex in which the substrate and GroES bind to GroEL by sharing seven common binding sites. 相似文献
87.
88.
Murata H Futami J Kitazoe M Yonehara T Nakanishi H Kosaka M Tada H Sakaguchi M Yagi Y Seno M Huh NH Yamada H 《Journal of biochemistry》2008,144(4):447-455
The glutathione S-transferase (GST)-fused protein expression system has been extensively used to generate a large quantity of proteins and has served for functional analysis in vitro. In this study, we developed a novel approach for the efficient intracellular delivery of GST-fused proteins into living cells to expand their usefulness up to in vivo use. Since protein cationization techniques are powerful strategies for efficient intracellular uptake by adsorptive-mediated endocytosis, GST-fused proteins were cationized by forming a complex with a polycationic polyethylenimine (PEI)-glutathione conjugate. On screening of protein transduction, optimized PEI-glutathione conjugate for protein transduction was characterized by a partly oligomerized mixture of PEI with average molecular masses of 600 (PEI600) modified with multiple glutathiones, which could have sufficient avidity for GST. Furthermore, enhanced endosomal escape of transduced GST-fused proteins was observed when they were delivered with a glutathione-conjugated PEI600 derivative possessing a hydroxybutenyl moiety. These results were confirmed by both intracellular confocal imaging of GST-fused green fluorescent protein and activation of an endogenous growth signal transduction pathway by a GST-fused constitutively active mutant of a kinase protein. These PEI-glutathione conjugates seem to be convenient molecular tools for protein transduction of widely used GST-fused proteins. 相似文献
89.
Brain Atrophy in a Murine Model of Chronic Fatigue Syndrome and Beneficial Effect of Hochu-ekki-to (TJ-41) 总被引:1,自引:0,他引:1
Chen R Moriya J Yamakawa J Takahashi T Li Q Morimoto S Iwai K Sumino H Yamaguchi N Kanda T 《Neurochemical research》2008,33(9):1759-1767
Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of chronic fatigue sydrome (CFS) and neuron
apoptosis. Nevertheless, no study has been performed directly to explore the relationship between CFS, BDNF and neuron apoptosis.
We induced a CFS model by six injections of killed Brucella abortus antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running activity, body weight (BW), ratio of cerebral
weight to BW (CW/BW) and expression levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily activity and
CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA expression levels in the hippocampus were suppressed in
the CFS model and TJ-41 treated mice, while no significant difference was found between them. We improved a murine model to
investigate the relationship between CFS and brain dysfunction. In this model, reduced daily activity might have been associated
with decreased hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41 increased the daily running
activity of the model, which was independent of brain recovery. 相似文献
90.
A Note on the Reactivation of the Fast Sodium Current in Spherical Clusters of Embryonic Chick Heart Cells 下载免费PDF全文
Reactivation of the fast sodium current in spherical clusters of embryonic chick heart cells was studied using the two-microelectrode voltage-clamp technique. The results show that there are at least two phases of reactivation. The contribution of the two phases to the overall reactivation process is highly dependent on the particular pulse protocol used to measure them. 相似文献