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991.
An improved method for the synthesis of enantiomerically pure D-cyclopentenyl nucleosides has been accomplished and their antiviral activity against orthopox viruses have been evaluated. The key intermediate, L-cyclopent-2-enone 13 was prepared from D-ribose using a ring closing metathesis reaction in eight steps. Among the synthesized nucleosides, the adenine 2 (Neplanocin A), cytosine 14, and 5-F-cytosine 15 analogues exhibited potent anti-orthopox virus activity, including smallpox virus. 相似文献
992.
Understanding the unique mechanism of L-FMAU (clevudine) against hepatitis B virus: molecular dynamics studies 总被引:3,自引:0,他引:3
The molecular dynamics simulation of HBV-polymerase.DNA.L-FMAU-TP complex demonstrated that L-FMAU-TP may not serve as a substrate for HBV polymerase because the appropriate binding of L-FMAU-TP to the active site of HBV polymerase may not take place without the unfavorable conformational adjustment, which prevents L-FMAU-TP from being incorporated into the growing viral DNA chain. 相似文献
993.
L-Nucleosides as chemotherapeutic agents 总被引:7,自引:0,他引:7
A genetic transformation system has been developed for three Mycosphaerella pathogens of banana and plantain (Musa spp.). Mycosphaerella fijiensis and Mycosphaerella musicola, the causal agents of black and yellow Sigatoka, respectively, and Mycosphaerella eumusae, which causes Septoria leaf spot of banana, were transformed with a construct carrying a synthetic gene encoding green fluorescent protein (GFP). Most single-spored transformants that expressed GFP constitutively were mitotically stable in the absence of selection for hygromycin B resistance. Transformants of all three species were pathogenic on the susceptible banana cultivar Grand Nain, and growth in planta was comparable to wild-type strains. GFP expression by transformants allowed us to observe extensive fungal growth within leaf tissue that eventually turned necrotic, at which point the fungi grew saprophytically on the dead tissue. Leaf chlorosis and necrosis were often observed in advance of saprophytic growth of the mycelium on necrotic tissue, which supports previous reports suggesting secretion of a phytotoxin. 相似文献
994.
Chu L Lo JL Yang YT Cheng K Smith RG Fisher MH Wyvratt MJ Goulet MT 《Bioorganic & medicinal chemistry letters》2001,11(4):515-517
The discovery of the potency-enhancing effect of 5-substitutions on the novel 2-arylindoles as nonpeptidyl GnRH receptor antagonists led to the identification of several analogues with high affinities on the GnRH receptor. The syntheses and SARs of these 5-substituted-2-arylindole analogues are reported. 相似文献
995.
Wei Yue Chu San Juan Cai Yong Yang Fu Fei Fei Li Ting Xu Han Qiu Qin Song Xu 《Acta Physiologiae Plantarum》2014,36(9):2491-2499
The rare earth elements are increasingly being used as trace supplements in different fields. In this study, subcellular distribution, the chemical forms and toxicity of cerium (Ce) were evaluated for Elodea canadensis. The effect of Ce (5–20 mg L?1) applied for 7 days was assessed by measuring changes in the nutrient elements, photosynthetic pigments, malondialdehyde and antioxidant systems. Ce accumulation was greatest in the cell walls, followed by the organelles and the soluble fraction. Ce levels were higher in cellulose and pectin than in other biomacromolecules. The toxic effects caused by Ce were shown by a reduction in photosynthetic pigments, disruption of nutrient elements, and increases in MDA content. E. canadensis shows Ce-induced oxidative stress by modulating antioxidant enzymes, such as guaiacol peroxidase and catalase. Elevated Ce levels may represent a potential risk for aquatic ecosystems. 相似文献
996.
Le Guo Runting Yin Kunmei Liu Xiaobo Lv Yonghong Li Xiangguo Duan Yuankui Chu Tao Xi Yingying Xing 《Applied microbiology and biotechnology》2014,98(8):3495-3507
Epitope vaccine is a promising option for prophylactic and therapeutic vaccination against Helicobacter pylori infection. Urease is an essential virulence factor and colonization factor for H. pylori. In this study, we constructed a multi-epitope vaccine named CTB-UE with mucosal adjuvant cholera toxin B subunit (CTB) and tandem copies of Th and B cell epitopes from H. pylori urease A and B subunits. The immunogenicity, specificity, ability to induce neutralizing antibodies against H. pylori urease, and prophylactic and therapeutic efficacy of the CTB-UE vaccine were evaluated in BALB/c mice model after purification. The experimental results indicated that CTB-UE could induce comparatively high levels of specific antibodies against native H. pylori urease, UreA, UreB, or the selected B cell epitopes UreA183–203 and UreB327–334 involved with the active site of urease and showed an effectively inhibitory effect on the enzymatic activity of urease. Besides, oral prophylactic or therapeutic immunization with CTB-UE significantly decreased H. pylori colonization compared with oral immunization with rUreB or PBS, and the protection was correlated with antigen-specific CD4+ T cells and IgG, IgA, and mucosal sIgA antibody responses. This CTB-UE vaccine may be a promising vaccine candidate for the control of H. pylori infection. 相似文献
997.
Medhat Rehan Teal Furnholm Ryan H. Finethy Feixia Chu Gomaah El-Fadly Louis S. Tisa 《Applied microbiology and biotechnology》2014,98(18):8005-8015
Several Frankia strains have been shown to be copper-tolerant. The mechanism of their copper tolerance was investigated for Frankia sp. strain EuI1c. Copper binding was shown by binding studies. Unusual globular structures were observed on the surface of the bacterium. These globular structures were composed of aggregates containing many relatively smaller “leaf-like” structures. Scanning electron microscopy with energy-dispersive X-ray (SEM-EDAX) analysis of these structures indicated elevated copper and phosphate levels compared to the control cells. Fourier transform infrared spectroscopy (FTIR) analysis indicated an increase in extracellular phosphate on the cell surface of copper-stressed cells. Bioinformatics’ analysis of the Frankia sp. strain EuI1c genome revealed five potential cop genes: copA, copZ, copC, copCD, and copD. Experiments with Frankia sp. strain EuI1c using qRT-PCR indicated an increase in messenger RNA (mRNA) levels of the five cop genes upon Cu2+ stress. After 5 days of Cu2+ stress, the copA, copZ, copC, copCD, and copD mRNA levels increased 25-, 8-, 18-, 18-, and 25-fold, respectively. The protein profile of Cu2+-stressed Frankia sp. strain EuI1c cells revealed the upregulation of a 36.7 kDa protein that was identified as FraEuI1c_1092 (sulfate-binding periplasmic transport protein). Homologues of this gene were only present in the genomes of the Cu2+-resistant Frankia strains (EuI1c, DC12, and CN3). These data indicate that copper tolerance by Frankia sp. strain EuI1c involved the binding of copper to the cell surface and transport proteins. 相似文献
998.
The 26th annual Barrels meeting was convened on the campus of the University of California San Diego, not far from the shores of the Pacific Ocean. The meeting focused on three main themes: the structure and function of the thalamic reticular nucleus, the neurovasculature system and its role in brain metabolism, and the origins and functions of cortical GABAergic interneurons. In addition to the major themes, there were short talks, a data blitz, and a poster session which highlighted the diversity and quality of the research ongoing in the rodent whisker-to-barrel system. 相似文献
999.
Alberto Muñoz Meiling Chu Peter I. Marris Uma S. Sagaram Jagdeep Kaur Dilip M. Shah Nick D. Read 《Molecular microbiology》2014,92(6):1357-1374
MsDef1 and MtDef4 from Medicago spp. are small cysteine‐rich defensins with potent antifungal activity against a broad range of filamentous fungi. Each defensin has a hallmark γ‐core motif (GXCX3–9C), which contains major determinants of its antifungal activity. In this study, the antifungal activities of MsDef1, MtDef4, and peptides derived from their γ‐core motifs, were characterized during colony initiation in the fungal model, Neurospora crassa. These defensins and their cognate peptides inhibited conidial germination and accompanying cell fusion with different potencies. The inhibitory effects of MsDef1 were strongly mediated by the plasma membrane localized sphingolipid glucosylceramide. Cell fusion was selectively inhibited by the hexapeptide RGFRRR derived from the γ‐core motif of MtDef4. Fluorescent labelling of this hexapeptide showed that it strongly bound to the germ tube plasma membrane/cell wall. Using N. crassa expressing the Ca2+ reporter aequorin, MsDef1, MtDef4 and their cognate peptides were each shown to perturb Ca2+ homeostasis in specific and distinct ways, and the disruptive effects of MsDef1 on Ca2+ were mediated by glucosylceramide. Together, our results demonstrate that MsDef1 and MtDef4 differ markedly in their antifungal properties and specific domains within their γ‐core motifs play important roles in their different modes of antifungal action. 相似文献
1000.