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231.
Daisuke Mori Hiroyuki Kimura Hidekazu Kawashima Yusuke Yagi Kenji Arimitsu Masahiro Ono Hideo Saji 《Bioorganic & medicinal chemistry》2019,27(18):4200-4210
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (99mTc) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent α4β2-nAChR agonist, we prepared A85380 derivatives labeled with 99mTc using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a 99mTc analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at α4β2-nAChR in both the docking simulation (?19.3 kcal/mol) and binding assay (Ki = 0.4 ± 0.04 nM). Further, 99mTc-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that 99mTc-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy. 相似文献
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Nakamura M Yagi N Kato T Fujita S Kawashima N Ehrhardt DW Hashimoto T 《The Plant journal : for cell and molecular biology》2012,71(2):216-225
Microtubules in eukaryotic cells are nucleated from ring-shaped complexes that contain γ-tubulin and a family of homologous γ-tubulin complex proteins (GCPs), but the subunit composition of the complexes can vary among fungi, animals and plants. Arabidopsis GCP3-interacting protein 1 (GIP1), a small protein with no homology to the GCP family, interacts with GCP3 in vitro, and is a plant homolog of vertebrate mitotic-spindle organizing protein associated with a ring of γ-tubulin 1 (MOZART1), a recently identified component of the γ-tubulin complex in human cell lines. In this study, we characterized two closely related Arabidopsis GIP1s: GIP1a and GIP1b. Single mutants of gip1a and gip1b were indistinguishable from wild-type plants, but their double mutant was embryonic lethal, and showed impaired development of male gametophytes. Functional fusions of GIP1a with green fluorescent protein (GFP) were used to purify GIP1a-containing complexes from Arabidopsis plants, which contained all the subunits (except NEDD1) previously identified in the Arabidopsis γ-tubulin complexes. GIP1a and GIP1b interacted specifically with Arabidopsis GCP3 in yeast. GFP-GIP1a labeled mitotic microtubule arrays in a pattern largely consistent with, but partly distinct from, the localization of the γ-tubulin complex containing GCP2 or GCP3 in planta. In interphase cortical arrays, the labeled complexes were preferentially recruited to existing microtubules, from which new microtubules were efficiently nucleated. However, in contrast to complexes labeled with tagged GCP2 or GCP3, their recruitment to cortical areas with no microtubules was rarely observed. These results indicate that GIP1/MOZART1 is an integral component of a subset of the Arabidopsis γ-tubulin complexes. 相似文献
234.
M. Hibi T. Kawashima T. Kasahara P.M. Sokolov S.V. Smirnov T. Kodera M. Sugiyama S. Shimizu K. Yokozeki J. Ogawa 《Letters in applied microbiology》2012,55(6):414-419
An Fe(II)/α‐ketoglutarate‐dependent dioxygenase, SadA, was obtained from Burkholderia ambifaria AMMD and heterologously expressed in Escherichia coli. Purified recombinant SadA had catalytic activity towards several N‐substituted l‐amino acids, which was especially strong with N‐succinyl l‐leucine. With the NMR and LC‐MS analysis, SadA converted N‐succinyl l‐leucine into N‐succinyl l‐threo‐β‐hydroxyleucine with >99% diastereoselectivity. SadA is the first enzyme catalysing β‐hydroxylation of aliphatic amino acid‐related substances and a potent biocatalyst for the preparation of optically active β‐hydroxy amino acids. 相似文献
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236.
Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors
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237.
Yamazaki T Okajima Y Kawashima H Tsukamoto A Sugiura J Shishido K 《Bioscience, biotechnology, and biochemistry》2006,70(6):1293-1299
The homobasidiomycete Coriolus hirsutus coding sequences of a lignin peroxidase (LiP) gene (lip, containing six (I-VI) introns), a lip cDNA (lipc), and three lipc derivatives containing one (I), three (I-III), or five (I-V) introns were inserted into chromosome-integrating expression vector. These recombinant plasmids were introduced into C. hirustus monokaryotic strain. The transformant carrying the promoter-lipc-terminator cassette did not contain enough mRNA molecules to be detectable by Northern-blot analysis. On the other hand, all the transformants carrying cassettes of genomic lip and intron(s)-containing lipc sequences contained sufficient amounts of mRNAs to be easily detected by Northern-blot analysis. LiP activities in the culture supernatants of these transformants were found to be about five times as high as those of transformants carrying the lipc cassette (or no cassette). The culture supernatants of the transformants with high LiP activity showed remarkably high conversion activity toward pentachlorophenol (PCP) and degradation activity toward 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD). These results indicate that at least one intron (intron I) is required for accumulation of lip mRNA and its subsequent translational expression in C. hirsutus. 相似文献
238.
Masahiro Ono Shun Hayashi Hiroyuki Kimura Hidekazu Kawashima Morio Nakayama Hideo Saji 《Bioorganic & medicinal chemistry》2009,17(19):7002-7007
We synthesized push–pull benzothiazole derivatives and evaluated their potential as β-amyloid imaging probes. In binding experiments in vitro, the benzothiazoles showed excellent affinity for synthetic Aβ(1-42) aggregates. β-Amyloid plaques in the mouse and human brain were clearly visualized with the benzothiazoles, reflecting the results in vitro. These compounds may be a useful scaffold for the development of novel PET/SPECT and fluorescent tracers for detecting β-amyloid in Alzheimer’s brains. 相似文献
239.
240.
Satoshi Niizuma Masao Tsukazaki Hitomi Suda Takeshi Murata Jun Ohwada Sawako Ozawa Hiroshi Fukuda Chikako Murasaki Masami Kohchi Kenji Morikami Kiyoshi Yoshinari Mika Endo Masako Ura Hiromi Tanimura Yoko Miyazaki Tsuyoshi Takasuka Akira Kawashima Eitaro Nanba Kounosuke Nakano Kotaro Ogawa Nobuo Shimma 《Bioorganic & medicinal chemistry letters》2009,19(7):2018-2021
Novel hexacyclic camptothecin analogs containing cyclic amidine, urea, or thiourea moiety were designed and synthesized based on the proposed 3D-structure of the topoisomerase I (Topo I)/DNA/camptothecin ternary complex. The analogs were prepared from 9-nitrocamptothecin via 7,9-diaminocamptothecin derivatives as a key intermediate. Among them, 7c exhibited in vivo antitumor activities superior to CPT-11 in human cancer xenograft models in mice at their maximum tolerated doses though its in vitro antiproliferative activity was comparable to SN-38 against corresponding cell lines. 相似文献