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排序方式: 共有327条查询结果,搜索用时 0 毫秒
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Tatsuya Maehigashi Seohyun Ahn Uk-Il Kim Jared Lindenberger Adrian Oo Pratibha C. Koneru Bijan Mahboubi Alan N. Engelman Mamuka Kvaratskhelia Kyungjin Kim Baek Kim 《PLoS pathogens》2021,17(7)
Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction. Consequently, STP0404 inhibits proper localization of HIV-1 RNA genomes in viral particles during viral maturation. Y99H and A128T mutations at the LEDGF/p75 binding pocket render resistance to STP0404. Extensive in vivo pharmacological and toxicity investigations demonstrate that STP0404 harbors outstanding therapeutic and safety properties. Overall, STP0404 is a potent and first-in-class ALLINI that targets LEDGF/p75 binding site and has advanced to a human trial. 相似文献
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A number of 2-hydroxy-6-methyl-7-(arylamino)-1,7-dihydropurin-8-ones have been synthesized. 3-Oxo-2-(arylhydrazono)butyric acid ethyl ester were acetylated and treated with triethyl amine and formamide in presence of 1,4-dioxane to yield N-(5-acetyl-4-ethoxy-2-oxo-2,5-dihydro-imidazol-1-yl)-N-arylacetamide, which on refluxation with urea and freshly prepared sodium ethoxide yielded the title compound. All the newly synthesized compounds have been characterized by spectroscopic and elemental analysis data. The synthesized compounds were screened against a representative panel of susceptible and resistant Gram-positive and Gram-negative bacteria using a standard antibiotic drug purinthol as control. Quantitative structure-activity relationship has also been interpreted in terms of correlation of biological activity with molecular refractive index parameters (M(R)) and Hammett substituent constant (sigma). 相似文献
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Nineteen efficient phosphate-solubilizing fluorescent Pseudomonas from the cold deserts of the trans-Himalayas were screened for stress tolerance against temperature, alkalinity, salinity,
calcium salts, and desiccation. Phylogenetic analysis based on 16S rRNA gene sequencing placed these bacteria under three
groups with fourteen strains in Group I including Pseudomonas trivialis and P. poae, two strains in Group II together with Pseudomonas kilonensis and P. corrugata, and three strains in Group III along with Pseudomonas jessenii and P. moraviensis. Genetic diversity assessed by ERIC and BOX-PCR revealed variability among strains belonging to the same phylogenetic groups.
Cluster analysis based on the growth characteristics under regimes of different stress levels placed the strains into three
distinct clusters displaying no correlation to their phylogenetic groups. Stress-tolerant strains differed in the level of
decline in phosphate solubilization under increasing intensity of various stress parameters. The highest decrease occurred
with 5% CaCO3, followed by 2.5% CaCO3, pH 11, 5% NaCl, temperature of 37°C, 40% PEG, 5% CaSO4, 2.5% NaCl, 2.5% CaSO4, pH 9 and temperature of 15°C. Two strains belonging to Phylogenetic Group I exhibited higher phosphate solubilization at
lower temperature. The results revealed that stress-tolerance ability was not limited to any particular phylogenetic group.
Knowledge about the genetic variants of phosphate-solubilizing fluorescent Pseudomonas with potential for tolerance to desiccation, alkalinity, temperature, and salinity could be useful in understanding their
ecological role under stressful environments of low phosphate availability. 相似文献
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RPNI, a combination of three commercially available growth media (RPMI-1640, NCTC-135 and IMDM) has been found to support long term continuous cultivation of 3D7 strain of Plasmodium falciparum in the presence of 10% bovine calf serum. During the present study, the suitability of this medium was evaluated for the development of P. falciparum in the presence of horse, goat and rabbit sera as well as various concentrations of ALBUMAX II. RPNI medium supplemented with 10% bovine calf serum (RPNI-BCS) was used as control. The cultures were maintained in candle jars protocol and parasitaemia was monitored daily up to day 7. Horse, goat and rabbit sera all supported the development of P. falciparum. Horse serum gave best results in RPNI medium and supported continuous culture up to day 100. The parasitaemia in the presence of ALBUMAX was significantly higher in RPNI than in RPMI-1640. Addition of hypoxanthine in RPMI-1640 caused an increase in parasitaemia whereas no obvious advantage could be observed in RPNI. The findings exhibited that medium RPNI has an edge over conventional RPMI-1640 medium for in vitro cultivation of P. falciparum. 相似文献
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Singh Ashish Tripathi Pratibha Yadawa Arun Kumar Singh Sarika 《Neurochemical research》2020,45(8):1731-1745
Neurochemical Research - Parkinson’s disease (PD) is a slow progressive, second most common neurodegenerative disease characterized by the loss of dopaminergic neurons from the nigrostriatal... 相似文献
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Vaccinia virus infection induces dendritic cell maturation but inhibits antigen presentation by MHC class II 总被引:2,自引:0,他引:2
Yao Y Li P Singh P Thiele AT Wilkes DS Renukaradhya GJ Brutkiewicz RR Travers JB Luker GD Hong SC Blum JS Chang CH 《Cellular immunology》2007,246(2):92-102
Vaccinia virus (VV) infection is known to inhibit dendritic cells (DC) functions in vitro. Paradoxically, VV is also highly immunogenic and thus has been used as a vaccine. In the present study, we investigated the effects of an in vivo VV infection on DC function by focusing on early innate immunity. Our data indicated that DC are activated upon in vivo VV infection of mice. Splenic DC from VV-infected mice expressed elevated levels of MHC class I and co-stimulatory molecules on their cell surface and exhibited the enhanced potential to produce cytokines upon LPS stimulation. DC from VV-infected mice also expressed a high level of interferon-beta. However, a VV infection resulted in the down-regulation of MHC class II expression and the impairment of antigen presentation to CD4 T cells by DC. Thus, during the early stage of a VV infection, although DC are impaired in some of the critical antigen presentation functions, they can promote innate immune defenses against viral infection. 相似文献
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