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991.
Chiung-Yao Huang Atallah F. Ahmed Jui-Hsin Su Ping-Jyun Sung Tsong-Long Hwang Pei-Lun Chiang Chang-Feng Dai Chih-Chuang Liaw Jyh-Horng Sheu 《Bioorganic & medicinal chemistry letters》2017,27(15):3267-3271
Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H–L (1–5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1–5 and a known compound sinubrasolide A (6) against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of compounds 1–6 were evaluated by measuring their ability to suppress N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils. 相似文献
992.
993.
Ji Hoon Song Ki Sung Kang You-Kyung Choi 《Bioorganic & medicinal chemistry letters》2017,27(23):5109-5113
Glutamate is the major excitatory neurotransmitter in the central nervous system and is involved in oxidative stress during neurodegeneration. In the present study, casuarinin prevented glutamate-induced HT22 murine hippocampal neuronal cell death by inhibiting intracellular reactive oxygen species (ROS) production. Moreover, casuarinin reduced chromatin condensation and annexin-V-positive cell production induced by glutamate. We also confirmed the underlying protective mechanism of casuarinin against glutamate-induced neurotoxicity. Glutamate markedly increased the phosphorylation of extracellular signal regulated kinase (ERK)-1/2 and p38, which are crucial in oxidative stress-mediated neuronal cell death. Conversely, treatment with casuarinin diminished the phosphorylation of ERK1/2 and P38. In conclusion, the results of this study suggest that casuarinin, obtained from natural products, acts as potent neuroprotective agent by suppressing glutamate-mediated apoptosis through the inhibition of ROS production and activation of the mitogen activated protein kinase (MAPK) pathway. Thus, casuarinin can be a potential therapeutic agent in the treatment of neurodegenerative diseases. 相似文献
994.
Dielectric screening effect of electronic polarization and intramolecular hydrogen bonding 下载免费PDF全文
Shen‐Shu Sung 《Protein science : a publication of the Protein Society》2017,26(10):2003-2009
Recent site‐resolved hydrogen exchange measurements have uncovered significant discrepancies between simulations and experimental data during protein folding, including the excessive intramolecular hydrogen bonds in simulations. This finding indicates a possibility that intramolecular charge–charge interactions have not included sufficient dielectric screening effect of the electronic polarization. Scaling down peptide atomic charges according to the optical dielectric constant is tested in this study. As a result, the number of intramolecular hydrogen bonds is lower than using unscaled atomic charges while reaching the same levels of helical contents or β‐hairpin backbone hydrogen bonds, because van der Waals interactions contribute substantially to peptide folding in water. Reducing intramolecular charge–charge interactions and hydrogen bonding increases conformational search efficiency. In particular, it reduces the equilibrium helical content in simulations using AMBER force field and the energy barrier in folding simulations using CHARMM force field. 相似文献
995.
Mingzhao Zhu Wayne D. Harshbarger Omar Robles Joanna Krysiak Kenneth G. Hull Sung Wook Cho Robyn D. Richardson Yanyan Yang Andres Garcia Lindsey Spiegelman Bianca Ramirez Christopher T. Wilson Ju Anne Yau James T. Moore Caitlen B. Walker James C. Sacchettini Wenshe R. Liu Stephan A. Sieber Daniel Romo 《Bioorganic & medicinal chemistry》2017,25(11):2901-2916
The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, β-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance. 相似文献
996.
X‐ray crystal structures of the pheromone‐binding domains of two quorum‐hindered transcription factors,YenR of Yersinia enterocolitica and CepR2 of Burkholderia cenocepacia 下载免费PDF全文
997.
Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy 下载免费PDF全文
998.
Estrogens and androgens inhibit association of RANKL with the pre‐osteoblast membrane through post‐translational mechanisms 下载免费PDF全文
999.
Jae-Jin Lee Yeon-Hee Lee Su-Jin Park Seung-Yeol Lee Sangkyu Park Dae Sung Lee In-Kyu Kang Leonid N. Ten Hee-Young Jung 《Antonie van Leeuwenhoek》2017,110(3):407-414
Strain 16F3HT, a Gram-negative, aerobic, non-motile, and oval-shaped bacterium, was isolated from river water collected from the Han River in South Korea. Growth of strain 16F3HT was observed at 10–42 °C (optimum at 25–30 °C), but no growth occurred at 4 °C. The strain is able to grow at pH 4–10 (optimum at pH 7–8) and tolerates up to 4% NaCl (w/v), with optimum growth at 0.5% NaCl. The isolate was found to be resistant to UV irradiation. Based on 16S rRNA gene sequence analysis, it is closely related to ‘Deinococcus seoulensis’ 16F1E (98.8%), Deinococcus aquaticus PB314T (98.1%) and Deinococcus caeni Ho-08T (98.0%). The level of DNA–DNA homology between the novel strain and the three related strains was 57.4, 41.2, and 35.8%, respectively. Chemotaxonomic data revealed that strain 16F3HT possesses MK-8 as the predominant respiratory quinone, an unidentified phosphoglycolipid as the major polar lipid, and C15:1 ω6c and C16:1 ω7c as the major fatty acids. The DNA G + C content was determined to be 65.7 mol%. Based on polyphasic evidence, strain 16F3HT (=KCTC 33794T = JCM 31406T) should be classified as the type strain of a novel Deinococcus species, for which the name Deinococcus knuensis sp. nov. is proposed. 相似文献
1000.
Dah Ihm Kim Ki Hoon Lee Ji Young Oh Jun Sung Kim Ho Jae Han 《Cellular and molecular neurobiology》2017,37(6):955-968
Mitochondria as dynamic organelles undergo morphological changes through the processes of fission and fusion which are major factors regulating their functions. A disruption in the balance of mitochondrial dynamics induces functional disorders in mitochondria such as failed energy production and the generation of reactive oxygen species, which are closely related to pathophysiological changes associated with Alzheimer’s disease (AD). Recent studies have demonstrated a relationship between abnormalities in mitochondrial dynamics and impaired mitochondrial function, clarifying the effects of morphofunctional aberrations which promote neuronal cell death in AD. Several possible signaling pathways have been suggested for a better understanding of the mechanism behind the key molecules regulating mitochondrial morphologies. However, the exact machinery involved in mitochondrial dynamics still has yet to be elucidated. This paper reviews the current knowledge on signaling mechanisms involved in mitochondrial dynamics and the significance of mitochondrial dynamics in controlling associated functions in neurodegenerative diseases, particularly in AD. 相似文献