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81.
82.
Takayuki Hattori Koyo Okitsu Norikazu Yamazaki Nobumichi Ohoka Norihito Shibata Takashi Misawa Masaaki Kurihara Yosuke Demizu Mikihiko Naito 《Bioorganic & medicinal chemistry letters》2017,27(18):4478-4481
We designed and synthesized hybrid molecules for a protein knockdown method based on the recognition of a His-tag fused to a protein of interest (POI). The synthesized target protein degradation inducers contained three functional moieties: a His-tag ligand (nickel nitrilotriacetic acid [Ni-NTA]), an E3 ligand (bestatin [BS] or MV1), and a carrier peptide (Tat or nonaarginine [R9]). The designed hybrid molecules, BS-Tat-Ni-NTA, MV1-Tat-Ni-NTA, BS-R9-Ni-NTA, and MV1-R9-Ni-NTA, efficiently degraded His-tagged cellular retinoic acid binding protein 2 via the ubiquitin–proteasome system (UPS). This system will become a useful tool for research into selective protein degradation inducers that act via the UPS. 相似文献
83.
Koyo Okitsu Takashi Misawa Takuji Shoda Masaaki Kurihara Yosuke Demizu 《Bioorganic & medicinal chemistry letters》2017,27(15):3417-3422
The fluorescent labeling of target proteins is useful for analyzing their functions and localization in cells, and several fluorescent probes have been developed. However, the fusion of tags such as green fluorescent protein (GFP) to target proteins occasionally affects their functions and/or localization in living cells. Therefore, an imaging method that uses short peptide tags such as hexa-histidine (the His tag) has been attracting increasing attention. Few studies have investigated ON/OFF switchable fluorescent probes for intracellular His-tagged proteins. We herein developed a novel ON/OFF switchable probe for imaging targeted intracellular proteins fused with a CH6 tag, which is composed of one cysteine residue and six histidine residues. 相似文献
84.
The taxonomy of Volvocales (Chlorophyceae, Chlorophyta) was traditionally based solely on morphological characteristics. However, because recent molecular phylogeny largely contradicts the traditional subordinal and familial classifications, no classification system has yet been established that describes the subdivision of Volvocales in a manner consistent with the phylogenetic relationships. Towards development of a natural classification system at and above the generic level, identification and sorting of hundreds of sequences based on subjective phylogenetic definitions is a significant step. We constructed an 18S rRNA gene phylogeny based on 449 volvocalean sequences collected using exhaustive BLAST searches of the GenBank database. Many chimeric sequences, which can cause fallacious phylogenetic trees, were detected and excluded during data collection. The results revealed 21 strongly supported primary clades within phylogenetically redefined Volvocales. Phylogenetic classification following PhyloCode was proposed based on the presented 18S rRNA gene phylogeny along with the results of previous combined 18S and 26S rRNA and chloroplast multigene analyses. 相似文献
85.
Hirabayashi A Mukaiyama H Kobayashi H Shiohara H Nakayama S Ozawa M Tsuji E Miyazawa K Misawa K Ohnota H Isaji M 《Bioorganic & medicinal chemistry》2008,16(20):9247-9260
Spleen tyrosine kinase (Syk) and zeta-associated protein kinase of 70k Da (ZAP-70) are members of the Syk family and non-receptor-type protein tyrosine kinases, which play crucial roles in B- and T-cell activation. Therefore, a Syk family tyrosine kinases inhibitor would be a useful therapeutic agent for the treatment of various allergic disorders and autoimmune diseases. Previously, we reported that 1,2,4-triazolo[4,3-c]pyrimidine derivative 1 and 1,2,4-triazolo[1,5-c]pyrimidine derivative 2 showed strong inhibitory activities against Syk family kinases. These compounds also exhibited high-level suppression of IL-2 in cellular assays. However, their oral efficacies were poor in a mouse model of IL-2 production. To improve oral effectiveness, we investigated a new series of Syk family kinases inhibitors. We found that imidazo[1,2-c]pyrimidine derivatives potently inhibited the Syk family kinases. Among these agents, compound 9f not only showed strong inhibitory activities against Syk and ZAP-70 kinases in vitro, but its oral administration resulted in the in vivo suppression of both the passive cutaneous anaphylaxis reaction and Concanavalin A-induced IL-2 production in a mouse model. 相似文献
86.
87.
Novel oligosaccharide has suppressive activity against human leukemia cell proliferation 总被引:1,自引:0,他引:1
Hosomi O Misawa Y Takeya A Matahira Y Sugahara K Kubohara Y Yamakura F Kudo S 《Glycoconjugate journal》2009,26(2):189-198
Various oligosaccharides containing galactose(s) and one glucosamine (or N-acetylglucosamine) residues with β1–4, α1–6 and β1–6 glycosidic bond were synthesized; Galβ1–4GlcNH2, Galα1–6GlcNH2, Galα1–6GlcNAc, Galβ1–6GlcNH2, Galβ1–4Galβ1–4GlcNH2 and Galβ1–4Galβ1–4GlcNAc. Galα1–6GlcNH2 (MelNH2) and glucosamine (GlcNH2) had a suppressive effect on the proliferation of K562 cells, but none of the other saccharides tested containing GlcNAc
showed this effect. On the other hand, the proliferation of the human normal umbilical cord fibroblast was suppressed by none
of the saccharides other than GlcNH2. Adding Galα1–6GlcNH2 or glucosamine to the culture of K562 cell, the cell number decreased strikingly after 72 h. Staining the remaining cells
with Cellstain Hoechst 33258, chromatin aggregation was found in many cells, indicating the occurrence of cell death. Furthermore,
all of the cells were stained with Galα1–6GlcNH-FITC (MelNH-FITC). Neither the control cells nor the cells incubated with
glucosamine were stained. On the other hand, when GlcNH-FITC was also added to cell cultures, some of them incubated with
Galα1–6GlcNH2 were stained. The difference in the stainability of the K562 cells by Galα1–6GlcNH-FITC and GlcNH-FITC suggests that the
intake of Galα1–6GlcNH2 and the cell death induced by this saccharide is not same as those of glucosamine. The isolation of the Galα1–6GlcNH2 binding protein was performed by affinity chromatography (melibiose-agarose) and LC-MS/MS, and we identified the human heterogeneous
ribonucleoprotein (hnRNP) A1 (34.3 kDa) isoform protein (30.8 kDa). The hnRNP A1 protein was also detected from the eluate(s)
of the MelNH-agarose column by the immunological method (anti-hnRNP-A1 and HRP-labeled anti-mouse IgG (γ) antibodies). 相似文献
88.
We investigated seasonal changes in dry mass and CO2 exchange rate in fruit and leaves of the evergreen tree Cinnamomum camphora with the aim of quantitatively determining the translocation balance between the two organs. The fruit dry mass growth peaked
in both August and October: the first increase was due to fruit pulp development and the second to seed development. Fruit
respiration also increased with the rapid increase in fruit dry mass. Therefore, the carbohydrates required for fruit development
showed two peaks during the reproductive period. Fruit photosynthesis was relatively high in early August, when fruit potentially
re-fixed 75% of respired CO2, indicating that fruit photosynthesis contributed 15–35% of the carbon requirement for fruit respiration. Current-year leaves
completed their growth in June when fruit growth began. Current-year leaves translocated carbohydrates at a rate of approximately
10–25 mg dry weight (dw) leaf−1 day−1 into other organs throughout the entire fruit growth period. This rate of translocation from current-year leaves was much
higher than the amount of carbohydrate required for reproduction (ca. 3 mg dw fruit−1 day−1). Given the carbon balance between fruit and current-year leaves, carbohydrates for reproduction were produced within the
current-year fruit-bearing shoots. C. camphora would be adaptive for steadily supplying enough amount of carbohydrate to the fruits, as there was little competition for
carbohydrates between the two organs. As assimilates by leaves are used for processes such as reproduction and the formation
of new shoots, photosynthesis by reproductive organs is considered to be important to compensate for reproductive cost. 相似文献
89.
Most in vitro protein synthesis systems require a supply of GTP for the formation of translation initiation complexes, with two GTP molecules per amino acid needed as an energy source for a peptide elongation reaction. In order to optimize protein synthesis reactions in a continuous‐flow wheat embryo cell‐free system, we have examined the influence of adding GTP and found that the system does not require any supply of GTP. We report here the preparation of a wheat embryo extract from which endogenous GTP was removed by gel filtration, and the influence of adding GTP to the system on protein synthesis reactions. Using Green Fluorescent Protein (GFP) as a reporter, higher levels of production were observed at lower concentrations of GTP, with the optimal level of production obtained with no supply of GTP. A HPLC‐based analysis of the extract and the translation mixture containing only ATP as an energy source revealed that GTP was not detectable in the extract, however, 35 μM of GTP was found in the translation mixture. This result suggests that GTP could be generated from other compounds, such as GDP and GMP, using ATP. A similar experiment with a C‐terminally truncated form of human protein tyrosine phosphatase 1B (hPTP1B1‐320) gave almost the same result. The wheat embryo cell‐free translation system worked most efficiently without exogenous GTP, producing 3.5 mg/mL of translation mixture over a 48‐h period at 26°C. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 相似文献
90.
Akihiro Tazumi Yuki Kakinuma Naoaki Misawa John E Moore Beverley C Millar Motoo Matsuda 《BMC microbiology》2009,9(1):256