排序方式: 共有18条查询结果,搜索用时 15 毫秒
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Naoki KANEKO Akinori NAKAMURA Yukihiko WASHIMI Takashi KATO Takashi SAKURAI Yutaka ARAHATA Masahiko BUNDO Akinori TAKEDA Shumpei NIIDA Kengo ITO Kenji TOBA Koichi TANAKA Katsuhiko YANAGISAWA 《Proceedings of the Japan Academy. Series B, Physical and biological sciences》2014,90(9):353-364
Alzheimer’s disease (AD) is the most common and devastating dementia. Simple and practical biomarkers for AD are urgently required for accurate diagnosis and to facilitate the development of disease-modifying interventions. The subjects for the study were selected on the basis of PiB amyloid imaging by PET. Forty PiB-positive (PiB+) individuals, including cognitively healthy controls (HC), and mild cognitive impairment and AD individuals, and 22 PiB-negative (PiB−) HC participated. Employing our novel highly sensitive immunoprecipitation-mass spectrometry, we measured plasma amyloid β-proteins (Aβs; Aβ1-40 and Aβ1-42) and Aβ-approximate peptides (AβAPs), which were cleaved from amyloid precursor protein (APP). Among the AβAPs, APP669-711 appeared to be a good reference for deciphering pathological change of Aβ1-42. We evaluated the performance of the ratio of APP669-711 to Aβ1-42 (APP669-711/Aβ1-42) as a biomarker. APP669-711/Aβ1-42 significantly increased in the PiB+ groups. The sensitivity and specificity to discriminate PiB+ individuals from PiB− individuals were 0.925 and 0.955, respectively. Our plasma biomarker precisely surrogates cerebral amyloid deposition. 相似文献
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Ryosuke Sugiyama Takahiro Nakatani Shinichi Nishimura Kei Takenaka Taro Ozaki Shumpei Asamizu Hiroyasu Onaka Hideaki Kakeya 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(38):13620-13625
Organisms often produce secondary metabolites as a mixture of biosynthetically related congeners. However, why are metabolites with minor chemical variations produced simultaneously? 5‐Alkyl‐1,2,3,4‐tetrahydroquinolines (5aTHQs) are small, lipophilic metabolites produced by Streptomyces nigrescens HEK616 when cultured with Tsukamurella pulmonis TP‐B0596. A mixture of 5aTHQs forms aggregates that show enhanced membrane affinity and biological activity. The ability to form aggregates and membrane‐binding activity is regulated by the length of the alkyl chains. Aggregates with long alkyl chains were too stable to fuse with lipid membranes. However, if inactive 5aTHQ congener was mixed with active congener, the mixture showed increased membrane affinity, enabling cellular entry and biological activity. Therefore, it is shown that sloppiness in a biosynthetic pathway, by which minor structural variations can be produced, is functionally rational, as the metabolites show synergistic action. 相似文献
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Asamizu S Xie P Brumsted CJ Flatt PM Mahmud T 《Journal of the American Chemical Society》2012,134(29):12219-12229
Sedoheptulose 7-phosphate cyclases are enzymes that utilize the pentose phosphate pathway intermediate, sedoheptulose 7-phosphate, to generate cyclic precursors of many bioactive natural products, such as the antidiabetic drug acarbose, the crop protectant validamycin, and the natural sunscreens mycosporine-like amino acids. These proteins are phylogenetically related to the dehydroquinate (DHQ) synthases from the shikimate pathway and are part of the more recently recognized superfamily of sugar phosphate cyclases, which includes DHQ synthases, aminoDHQ synthases, and 2-deoxy-scyllo-inosose synthases. Through genome mining and biochemical studies, we identified yet another subset of DHQS-like proteins in the actinomycete Actinosynnema mirum and the myxobacterium Stigmatella aurantiaca DW4/3-1. These enzymes catalyze the conversion of sedoheptulose 7-phosphate to 2-epi-valiolone, which is predicted to be an alternative precursor for aminocyclitol biosynthesis. Comparative bioinformatics and biochemical analyses of these proteins with 2-epi-5-epi-valiolone synthases (EEVS) and desmethyl-4-deoxygadusol synthases (DDGS) provided further insights into their genetic diversity, conserved amino acid sequences, and plausible catalytic mechanisms. The results further highlight the uniquely diverse DHQS-like sugar phosphate cyclases, which may provide new tools for chemoenzymatic, stereospecific synthesis of various cyclic molecules. 相似文献
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Bond Formation and Coupling between Germyl and Bridging Germylene Ligands in Dinuclear Palladium(I) Complexes 下载免费PDF全文
Dr. Makoto Tanabe Shumpei Omine Naoko Ishikawa Prof. Dr. Kohtaro Osakada Yoshihiro Hayashi Prof. Dr. Susumu Kawauchi 《Angewandte Chemie (International ed. in English)》2015,54(9):2679-2683
The dinuclear palladium(I) complexes [L(Ar2HGe)Pd(μ‐GeAr2)2Pd(GeHAr2)L] (Ar=Ph, p‐Tol; L=PMe3, tBuNC) contain terminal germyl and bridging germylene ligands with the experimentally observed Ge???Ge bond lengths of 2.8263(4) Å (L=PMe3) and 2.928(1) Å (L=tBuNC), which are close to the longest Ge? Ge bond reported to date [2.714(1) Å]. Significant Ge???Ge interactions between the germylene and germyl ligands (PMe3 complexes > tBuNC complexes) are supported by DFT calculations, Wiberg bond indices (WBI), and natural bond orbital (NBO) analyses. Exchanging tBuNC for PMe3 ligands increases the Ge???Ge interaction, and simultaneously activates two Pd? Ge bonds. Adding the chelating diphosphine 1,2‐bis(diethylphosphino)ethane (depe) to the PMe3 complexes results in the intramolecular coupling of germyl and germylene ligands followed by extrusion of a digermane. 相似文献
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Hidenobu Tsuji Takayuki Nakano Yoshihiro Matsumoto Shumpei Kameyama 《Optical Review》2016,23(2):155-160
We have developed an illumination optical system for 3D imaging ladar (laser detection and ranging) which forms flattop beam shape by transformation of the Gaussian beam in the wide distance range. The illumination is achieved by beam division and recombination using a prism and a negative powered lens. The optimum condition of the transformation by the optical system is derived. It is confirmed that the flattop distribution can be formed in the wide range of the propagation distance from 1 to 1000 m. The experimental result with the prototype is in good agreement with the calculation result. 相似文献
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Chiva C Barthe P Codina A Gairí M Molina F Granier C Pugnière M Inui T Nishio H Nishiuchi Y Kimura T Sakakibara S Albericio F Giralt E 《Journal of the American Chemical Society》2003,125(6):1508-1517
The total synthesis and structural characterization of the MHCII-associated p41 invariant chain fragment (P41icf) is described. P41icf plays a crucial role in the maturation of MHC class II molecules and antigen processing, acting as a highly selective cathepsin L inhibitor. P41icf synthesis was achieved using a combined solid-phase/solution approach. The entire molecule (65 residues, 7246 Da unprotected) was assembled in solution from fully protected peptides in the size range of 10 residues. After deprotection, oxidative folding in carefully adjusted experimental conditions led to the completely folded and functional P41icf with a disulfide pairing identical to that of native P41icf. CD, NMR, and surface plasmon resonance (SPR) were used for the structural and functional characterization of synthetic P41icf. CD thermal denaturation showed clear cooperative behavior. Tight cathepsin L binding was demonstrated by SPR. (1)H NMR spectroscopy at 800 MHz of unlabeled P41icf was used to solve the three-dimensional structure of the molecule. P41icf behaves as a well-folded protein domain with a topology very close to the crystallographic cathepsin L-bound form. 相似文献
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Shumpei Asamizu 《Tetrahedron letters》2006,47(4):473-475
Indole-3-pyruvic acid was transformed to chromopyrrolic acid by a novel heme-containing enzyme StaD responsible for staurosporine biosynthetic pathway in Streptomyces sp. TP-A0274. 相似文献