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991.
Tamio Ueno Norio Kurihara Shigeru Hashimoto Minoru Nakajima 《Bioscience, biotechnology, and biochemistry》2013,77(11):1343-1350
By means of a modified Königs-Knorr reaction using 2,3,4,6-tetra-O-benzyl-D-gluco- pyranosyl chloride, all the possible isomers of d-glucopyranoside of trans-2-aminocyclo- hexanol were synthesized. The total yield of the α-anomers exceeded that of the corresponding β-anomers.Treatment of methyl tri-O-acetyl-6-azido-6-deoxy-d-glucopyranoside (II) with benzyl chloride afforded the corresponding tri-O-benzyl derivative. Reduction of the azido group with zinc-acetic acid or sodium amalgam gave 6-amino derivative. N-Acetylation, hydrolysis of the I-O-methyl group, acetylation and treatment with dry hydrogen chloride in dioxane afforded the title compound (VIII). Königs-Knorr reaction of the chloride with (+)- and (?)-2-aminocyclohexanol produced the corresponding glycosides, one of which was proved to have the α-configuration. 相似文献
992.
Hiroyuki Kawashima Youhei Sohma Tomoya Nakanishi Hitomi Kitamura Hidehito Mukai Masayuki Yamashita Kenichi Akaji Yoshiaki Kiso 《Bioorganic & medicinal chemistry》2013,21(21):6323-6327
Inhibition of amyloid β peptide (Aβ) aggregation is a potential therapeutic approach to treat Alzheimer’s disease. We report that an O-acyl isopeptide of Aβ1–42 (1) containing an ester bond at the Gly25-Ser26 moiety inhibits Aβ1–42 fibril formation at equimolar ratio. Inhibitory activity was retained by an N-Me-β-Ala26 derivative (2), in which the ester of 1 was replaced with N-methyl amide to improve chemical stability at physiological pH. Inhibition was verified by fluorescence anisotropy, Western blot, and atomic force microscopy. This report suggests a new class of Aβ aggregation inhibitor based on modification of Aβ1–42 at Gly25-Ser26. 相似文献
993.
From investigation of 2000 soil isolates, we identified two serine-type amidohydrolases that can hydrolyze d-aminoacyl derivatives from the culture supernatant of Streptomyces species 82F2 and 83D12. The enzymes, redesignated as 82F2-DAP and 83D12-DAP, were purified for homogeneity and characterized. Each enzyme had molecular mass of approximately 40 kDa, and each showed moderate stability with respect to temperature and pH. Among hydrolytic activities toward d-aminoacyl-pNAs, the enzymes showed strict specificity toward d-Phe-pNA, but showed broad specificity toward d-aminoacyl esters. The specific activity for d-Phe-pNA hydrolysis of 82F2-DAP was ten-fold higher than that of 83D12-DAP. As a second function, each enzyme showed peptide bond formation activity by its function of aminolysis reaction. Based on results of d-Phe-d-Phe synthesis under various conditions, we propose a reaction mechanism for d-Phe-d-Phe production. Furthermore, the enzymes exhibited peptide elongation activity, producing oligo homopeptide in a one-pot reaction. We cloned the genes encoding each enzyme, which revealed that the primary structure of each enzyme showed 30-60% identity with those of peptidases belonging to the clan SE, S12 peptidase family categorized as serine peptidase with d-stereospecificity. 相似文献
994.
Rafiq K Sherajee SJ Fan YY Fujisawa Y Takahashi Y Matsuura J Hase N Urata H Nakano D Hitomi H Nishiyama A 《The Chinese journal of physiology》2011,54(1):30-35
A growing body of evidence suggests the potential role of chymase in organ injury in diabetes. We investigated blood glucose levels and survival in transgenic mice carrying the human chymase gene (Tg). Intraperitoneal injections of streptozotocin (STZ) (200, 100, 75 and 50 mg/kg in total, i.p.) were given to uninephrectomized Tg mice and wild-type C57BL/6 (BL) mice. Before STZ injection, the Tg mice had significantly lower body weights and slightly higher systolic blood pressure as compared with the BL mice. STZ-treated Tg mice showed significantly higher postprandial blood glucose levels as compared with the STZ-treated BL mice. The survival prevalence of STZ-treated Tg mice was zero, whereas BL mice showed a value of 40% until 42 days. STZ (100, 75 or 50 mg/kg, i.p.)-treated Tg mice also showed a similar pattern as compared with the STZ-treated BL mice. These data suggest that human chymase contributes to blood glucose levels and mortality during the progression of diabetes. 相似文献
995.
Hitomi H Mehta PK Taniyama Y Lassègue B Seidel-Rogol B San Martin A Griendling KK 《American journal of physiology. Cell physiology》2011,301(6):C1415-C1422
Angiotensin II (ANG II) has been implicated in the pathogenesis of diabetic micro- and macrovascular disease. In vascular smooth muscle cells (VSMCs), ANG II phosphorylates and degrades insulin receptor substrate-1 (IRS-1). While the pathway responsible for IRS-1 degradation in this system is unknown, c-Jun NH(2)-terminal kinase (JNK) has been linked with serine phosphorylation of IRS-1 and insulin resistance. We investigated the role of JNK in ANG II-induced IRS-1 phosphorylation, degradation, Akt activation, glucose uptake, and hypertrophic signaling, focusing on three IRS-1 phosphorylation sites: Ser302, Ser307, and Ser632. Maximal IRS-1 phosphorylation on Ser632 occurred at 5 min, on Ser307 at 30 min, and on Ser302 at 60 min. The JNK inhibitor SP600125 reduced ANG II-induced IRS-1 Ser307 phosphorylation (by 80%), IRS-1 Ser302 phosphorylation (by 70%), and IRS-1 Ser632 phosphorylation (by 50%). However, JNK inhibition had no effect on ANG II-mediated IRS-1 degradation, nor did it reverse the ANG II-induced decrease in Akt phosphorylation or glucose uptake. Transfection of VSMCs with mutants S307A, S302A, or S632A of IRS-1 did not block ANG II-mediated IRS-1 degradation. In contrast, JNK inhibition attenuated insulin-induced upregulation of collagen and smooth muscle α-actin in ANG II-pretreated cells. We conclude that phosphorylation of Ser307, Ser302, and Ser632 of IRS-1 is not involved in ANG II-mediated IRS-1 degradation, and that JNK alone does not mediate ANG II-stimulated IRS-1 degradation, but rather is responsible for the hypertrophic effects of insulin on smooth muscle. 相似文献
996.
997.
Traditional neurological models of language were based on a single neural pathway (the dorsal pathway underpinned by the arcuate fasciculus). Contemporary neuroscience indicates that anterior temporal regions and the "ventral" language pathway also make a significant contribution, yet there is no computationally-implemented model of the dual pathway, nor any synthesis of normal and aphasic behavior. The "Lichtheim 2" model was implemented by developing a new variety of computational model which reproduces and explains normal and patient data but also incorporates neuroanatomical information into its architecture. By bridging the "mind-brain" gap in this way, the resultant "neurocomputational" model provides a unique opportunity to explore the relationship between lesion location and behavioral deficits, and to provide a platform for simulating functional neuroimaging data. 相似文献
998.
Murakami T Kamikado N Fujimoto R Hamaguchi K Nakamura H Chijiwa T Ohno M Oda-Ueda N 《Bioscience, biotechnology, and biochemistry》2011,75(5):864-870
Protobothrops flavoviridis venom contains plural phospholipase A(2) (PLA(2)) isozymes. A [Lys(49)]PLA(2) called BPII induced cell death in human leukemia cells. PLA2, an [Asp(49)]PLA(2) that has much stronger lipolytic activity than BPII, failed to induce cell death. BPII-treated cells showed morphological changes, DNA fragmentation, and nuclear condensation. This BPII-induced apoptotic cell death was neither inhibited by inhibitors of caspases 3 and 6 nor accompanied by activation of procaspase 3, indicating that BPII-induced cell death is caspase independent. Since inactive p-bromophenacylated BPII induced cell death, BPII-induced apoptotic cell death is independent of PLA(2) lipolytic activity. Rapid externalization of phosphatidylserine in BPII-treated cells was observed for fluorescein isothiocyanate (FITC)-labeled annexin V. In the cells treated with BPII, this spread over the cell membranes, implying that the cell toxicity of BPII is mediated via its cell-surface receptor. 相似文献
999.
Transglutaminase (TGase) is a family of enzymes that catalyzes cross-linking reaction between glutamine- and lysine residue
of substrate proteins in several mammalian biological events. Substrate proteins for TGase and their physiological relevance
have been still in research, continuously expanding. In this study, we have established a novel screening system that enables
identification of cDNA sequence encoding favorable primary structure as a substrate for tissue-type transglutaminase (TGase
2), a multifunctional and ubiquitously expressing isozyme. By the screening, we identified several T7 phage clones that displayed
substrate peptides for TGase 2 as a translated product from human brain cDNA library. Among the selected clones, the C-terminal
region of IKAP, IkappaB kinase complex associated protein, appeared as a highly reactive substrate sequence for TGase 2. This
system will open possibility of rapid identification of substrate sequences for transglutaminases at a genetic level. 相似文献
1000.
Loudet A Ueno Y Wu L Jose J Barhoumi R Burghardt R Burgess K 《Bioorganic & medicinal chemistry letters》2011,21(6):1849-1851
A dye cassette fluoresces green (ca 520 nm) in the cytoplasm, endoplasmic reticulum (ER), and lysosomes, but red in mitochondria, that is, it illustrates ‘organelle specific energy transfer’. This phenomenon may open new horizons in intracellular imaging. 相似文献