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81.
Jayaraman Selvaraj Veeraraghavan Vishnupriya Hussain Sardar Janardhana Papayya Balakrishna Josephine Rex Surapaneni Krishna Mohan Periyasamy Vijayalakshmi Rajagopal Ponnulakshmi 《Bioinformation》2020,16(11):801
Beta-catenin is linked with colorectal cancer (CRC). Therefore, it is of interest to design and develop novel compounds to combat CRC. Hence, we document compounds (chlorogenic acid, gallic acid, protocatechuic acid, quercetin and vanillic acid) from Lycopersicon esculentum with optimal binding features for further consideration. 相似文献
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84.
Protein tyrosine phosphatase 1B (PTP1B) is involved in the down-regulation of insulin signaling and is a well-validated therapeutic target for the treatment of diabetes and obesity. Key to the design of potent inhibitors of PTP1B is a moiety that effectively mimics the phosphate group of the natural phosphotyrosine substrate. Difluoromethylsulfonomethylphenylalanine (F(2)Smp) is one of the best monoanionic pTyr mimics reported to date. However, the difluoromethylenesulfonic acid (DFMS) group as a phosphate mimic has not been carefully evaluated in the context of a non-peptidyl platform. Here we present a careful examination of the DFMS group as a phosphate mimic. This was achieved by first constructing an analog of a previously reported high affinity, non-peptidyl PTP1B inhibitor (compound 2, IC(50)=8nM) in which a difluoromethylenephosphonic acid group is replaced with the DFMS moiety (compound 6). We also report the synthesis of its non-fluorinated methylenesulfonic analog (compound 7), as well as two other derivatives in which a distal sulfonamide moiety is replaced with a difluoromethylenesulfonamide group (compounds 8 and 9). Compounds 2 and 6-9 were examined as PTP1B inhibitors. Replacing the distal sulfonamide moiety with a difluoromethylenesulfonamide group had only a modest effect on inhibitor potency. However, compound 6 was approximately a 1000-fold poorer inhibitor than compound 2. Most significantly, inhibition studies with compound 7 and a peptide bearing sulfonomethylphenylalanine revealed that the fluorines have little effect on the potency of the DFMS-bearing inhibitors. This is in contrast to a previous assumption that the fluorines in DFMS-bearing inhibitors contributed significantly to their potency. This may in part explain the large difference in potency between the DFMS and DFMP-bearing compounds. These results also demonstrate that sulfonomethylphenylalanine, a pTyr mimic that is readily constructed, is a relatively good pTyr mimic in comparison to most others that have been reported when examined in the context of the DADE-X-LNH(2) peptide platform. 相似文献
85.
Shafiq Ullah Fiaz Ahmed Amin Badshah Ataf Ali Altaf Ramsha Raza Bhajan Lal Rizwan Hussain 《PloS one》2013,8(10)
Nano materials with high surface area increase the kinetics and extent of the redox reactions, thus resulting in high power and energy densities. In this study high surface area zinc oxide nanorods have been synthesized by surfactant free ethylene glycol assisted solvothermal method. The nanorods thus prepared have diameters in the submicron range (300∼500 nm) with high aspect ratio. They have uniform geometry and well aligned direction. These nanorods are characterized by XRD, SEM, Specific Surface Area Analysis, solubility in alkaline medium, EDX analysis and galvanostatic charge/discharge studies in Zn/AgO batteries. The prepared zinc oxide nanorods have low solubility in alkaline medium with higher structural stability, which imparts the improved cycle life stability to Zn/AgO cells. 相似文献
86.
RNA interference (RNAi) is a homology-dependent gene silencing technology that involves double-stranded RNA directed against a target gene or its promoter region. Using hairpin constructs, double-stranded RNA can be expressed in plants relatively easily, enabling this technology to be applied to a wide range of species to silence the expression of both specific endogenous genes and genes of invading pathogens. RNAi has also been used to engineer metabolic pathways to overproduce secondary products with health, yield or environmental benefits. The application of tissue-specific or inducible gene silencing, with the use of appropriate promoters, and the ability to silence several genes simultaneously should enhance our ability to create novel traits in plants. 相似文献
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88.
Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly 总被引:15,自引:0,他引:15
Apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) are necessary for lipoprotein assembly. ApoB consists of five structural domains, betaalpha(1)-beta(1)-alpha(2)-beta(2)-alpha(3). We propose that MTP contains three structural motifs (N-terminal beta-barrel, central alpha-helix, and C-terminal lipid cavity) and three functional domains (lipid transfer, membrane associating, and apoB binding). MTP's lipid transfer activity is required for the assembly of lipoproteins. This activity renders nascent apoB secretion-competent and may be involved in the import of triglycerides into the lumen of endoplasmic reticulum. In addition, MTP binds to apoB with high affinity involving ionic interactions. MTP interacts at multiple sites in the N-terminal betaalpha(1) structural domain of apoB. A novel antagonist that inhibits apoB-MTP binding decreases apoB secretion. Furthermore, site-directed mutagenesis and deletion analyses that inhibit apoB-MTP binding decrease apoB secretion. Lipids modulate protein-protein interactions between apoB and MTP. Lipids associated with MTP increase apoB-MTP binding whereas lipids associated with apoB decrease this binding. Thus, specific antagonist, site-directed mutagenesis, deletion analyses, and modulation studies support the notion that apoB-MTP binding plays a role in lipoprotein biogenesis. However, specific steps in lipoprotein assembly that require apoB-MTP binding have not been identified. ApoB-MTP binding may be important for the prevention of degradation and lipidation of nascent apoB. 相似文献
89.
Aims: Starvation stress is a condition that nonstarter lactic acid bacteria (NSLAB) normally encounter. This study was aimed to investigate starvation-induced proteins in Lactobacillus casei during stationary growth phase.
Methods and Results: The impact of carbohydrate starvation on L. casei GCRL163 was investigated using two different media (a modified de Man, Rogosa and Sharpe broth and a semi-defined medium). Cells were grown in the presence of excess lactose (1%) or starvation (0%) and differences in the patterns of one-dimensional sodum dodecyl sulfate–polyacrylamide gel electrophoresis and two-dimensional electrophoresis of the cytosolic protein fractions were investigated. Differentially regulated proteins were identified by MALDI-TOF/TOF mass spectrometry. Many differentially regulated proteins were enzymes of various metabolic pathways involved in carbohydrate metabolism to yield energy. Differences in protein expression were also observed in the two culture conditions tested in this experiment.
Conclusion: Numerous glycolytic enzymes were differentially regulated under lactose starvation. The differential expression of these glycolytic enzymes suggests a potential survival strategy under harsh growth conditions (i.e. lactose starvation).
Significance and Impact of the Study: This paper reports improved understanding of stress responses and survival mechanism of NSLAB under lactose-depleted cheese-ripening condition. This knowledge of how NSLAB bacteria adapt to lactose starvation could be applied to predict the performances of bacteria in other industrial applications. 相似文献
Methods and Results: The impact of carbohydrate starvation on L. casei GCRL163 was investigated using two different media (a modified de Man, Rogosa and Sharpe broth and a semi-defined medium). Cells were grown in the presence of excess lactose (1%) or starvation (0%) and differences in the patterns of one-dimensional sodum dodecyl sulfate–polyacrylamide gel electrophoresis and two-dimensional electrophoresis of the cytosolic protein fractions were investigated. Differentially regulated proteins were identified by MALDI-TOF/TOF mass spectrometry. Many differentially regulated proteins were enzymes of various metabolic pathways involved in carbohydrate metabolism to yield energy. Differences in protein expression were also observed in the two culture conditions tested in this experiment.
Conclusion: Numerous glycolytic enzymes were differentially regulated under lactose starvation. The differential expression of these glycolytic enzymes suggests a potential survival strategy under harsh growth conditions (i.e. lactose starvation).
Significance and Impact of the Study: This paper reports improved understanding of stress responses and survival mechanism of NSLAB under lactose-depleted cheese-ripening condition. This knowledge of how NSLAB bacteria adapt to lactose starvation could be applied to predict the performances of bacteria in other industrial applications. 相似文献
90.
Michael Eddleston Peter Eyer Franz Worek Edmund Juszczak Nicola Alder Fahim Mohamed Lalith Senarathna Ariyasena Hittarage Shifa Azher K. Jeganathan Shaluka Jayamanne Ludwig von Meyer Andrew H. Dawson Mohamed Hussain Rezvi Sheriff Nick A. Buckley 《PLoS medicine》2009,6(6)