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排序方式: 共有396条查询结果,搜索用时 15 毫秒
71.
Massah AR Adibi H Khodarahmi R Abiri R Majnooni MB Shahidi S Asadi B Mehrabi M Zolfigol MA 《Bioorganic & medicinal chemistry》2008,16(10):5465-5472
Silica sulfuric acid catalyzes efficiently the reaction of sulfonamides with both carboxylic acid anhydrides and chlorides under solvent-free and heterogeneous conditions. All the reactions were done at room temperature and the N-acylsulfonamides were obtained with high yields and purity via an easy work-up procedure. This method is attractive and is in a close agreement with green chemistry. These compounds were also investigated for antibacterial activity, including Gram-positive cocci and Gram-negative bacilli, and carbonic anhydrase II inhibitory activity. 相似文献
72.
Dysbindin was identified as a dystrobrevin-binding protein potentially involved in the pathogenesis of muscular dystrophy. Subsequently, genetic studies have implicated variants of the human dysbindin-encoding gene, DTNBP1, in the pathogeneses of Hermansky-Pudlak syndrome and schizophrenia. The protein is a stable component of a multisubunit complex termed BLOC-1 (biogenesis of lysosome-related organelles complex-1). In the present study, the significance of the dystrobrevin-dysbindin interaction for BLOC-1 function was examined. Yeast two-hybrid analyses, and binding assays using recombinant proteins, demonstrated direct interaction involving coiled-coil-forming regions in both dysbindin and the dystrobrevins. However, recombinant proteins bearing the coiled-coil-forming regions of the dystrobrevins failed to bind endogenous BLOC-1 from HeLa cells or mouse brain or muscle, under conditions in which they bound the Dp71 isoform of dystrophin. Immunoprecipitation of endogenous dysbindin from brain or muscle resulted in robust co-immunoprecipitation of the pallidin subunit of BLOC-1 but no specific co-immunoprecipitation of dystrobrevin isoforms. Within BLOC-1, dysbindin is engaged in interactions with three other subunits, named pallidin, snapin and muted. We herein provide evidence that the same 69-residue region of dysbindin that is sufficient for dystrobrevin binding in vitro also contains the binding sites for pallidin and snapin, and at least part of the muted-binding interface. Functional, histological and immunohistochemical analyses failed to detect any sign of muscle pathology in BLOC-1-deficient, homozygous pallid mice. Taken together, these results suggest that dysbindin assembled into BLOC-1 is not a physiological binding partner of the dystrobrevins, likely due to engagement of its dystrobrevin-binding region in interactions with other subunits. 相似文献
73.
Ramin Amirnovin 《Journal of molecular evolution》1997,44(5):473-476
A computer program was used to test Wong's coevolution theory of the genetic code. The codon correlations between the codons
of biosynthetically related amino acids in the universal genetic code and in randomly generated genetic codes were compared.
It was determined that many codon correlations are also present within random genetic codes and that among the random codes
there are always several which have many more correlations than that found in the universal code. Although the number of correlations
depends on the choice of biosynthetically related amino acids, the probability of choosing a random genetic code with the
same or greater number of codon correlations as the universal genetic code was found to vary from 0.1% to 34% (with respect
to a fairly complete listing of related amino acids). Thus, Wong's theory that the genetic code arose by coevolution with
the biosynthetic pathways of amino acids, based on codon correlations between biosynthetically related amino acids, is statistical
in nature.
Received: 8 August 1996 / Accepted: 26 December 1996 相似文献
74.
Ramin Ekhteiari Salmas Murat Senturk Mine Yurtsever 《Journal of enzyme inhibition and medicinal chemistry》2016,31(3):425-433
Carbonic anhydrase type IX (CA IX) enzyme is mostly over expressed in different cancer cell lines and tumor tissues. Potent CA IX inhibitors can be effective for adjusting the pH imbalance in tumor cells. In the present work, we represented the successful application of high throughput virtual screening (HTVS) of large dataset from ZINC database included of ~7 million compounds to discover novel inhibitors of CA IX. HTVS and molecular docking were performed using consequence Glide/standard precision (SP), extra precision (XP) and induced fit docking (IFD) molecular docking protocols. For each compound, docking code calculates a set of low-energy poses and then exhaustively scans the binding pocket of the target with small compounds. Novel CA IX inhibitor candidates were suggested based on molecular modeling studies and a few of them were tested using in vitro analysis. These compounds were determined as good inhibitors against human CA IX target with Ki in the range of 0.85–1.58?μM. In order to predict the pharmaceutical properties of the selected compounds, ADME (absorption, distribution, metabolism and excretion) analysis was also carried out. 相似文献
75.
Faghih R Dwight W Pan JB Fox GB Krueger KM Esbenshade TA McVey JM Marsh K Bennani YL Hancock AA 《Bioorganic & medicinal chemistry letters》2003,13(7):1325-1328
Novel 4'-[(NR1R2-1-yl)]-propoxy-biaryl-4-carboxamides were designed and synthesized. All compounds were tested for affinity at histamine H(3)receptors. Most compounds were highly potent and selective for human and rat H(3) receptors and selected examples such as A-349821 showed functional antagonism of H(3) receptors in vitro and in a mouse dipsogenia model. 相似文献
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79.
Humor processing involves distinct processing stages including incongruity detection, emotional response, and engagement of mesolimbic reward regions. Dysfunctional reward processing and clinical symptoms in response to humor have been previously described in both hypocretin deficient narcolepsy-cataplexy (NC) and in idiopathic Parkinson disease (PD). For NC patients, humor is the strongest trigger for cataplexy, a transient loss of muscle tone, whereas dopamine-deficient PD-patients show blunted emotional responses to humor. To better understand the role of reward system and the various contributions of hypocretinergic and dopaminergic mechanisms to different stages of humor processing we examined the electrophysiological response to humorous and neutral pictures when given as reward feedback in PD, NC and healthy controls. Humor compared to neutral feedback demonstrated modulation of early ERP amplitudes likely corresponding to visual processing stages, with no group differences. At 270 ms post-feedback, conditions showed topographical and amplitudinal differences for frontal and left posterior electrodes, in that humor feedback was absent in PD patients but increased in NC patients. We suggest that this effect relates to a relatively early affective response, reminiscent of increased amygdala response reported in NC patients. Later ERP differences, corresponding to the late positive potential, revealed a lack of sustained activation in PD, likely due to altered dopamine regulation in reward structures in these patients. This research provides new insights into the temporal dynamics and underlying mechanisms of humor detection and appreciation in health and disease. 相似文献
80.
Organic osmolytes are used in animal and plant cells to adapt to hyper- and hypoosmolar stress. We used our RBC-membrane model to investigate the effects of the osmolytes betaine, sorbitol and myo-inositol on Na(+)/K(+)-ATPase, Ca(2+)-ATPase and calmodulin-stimulated Ca(2+)-ATPase (CaM). Our results show that betaine inhibited ATPases by more than 61%: Na(+)/K(+)-ATPase (75 +/- 5.9 vs 27 +/- 2.2), Ca(2+)-ATPase (236 +/- 18.9 vs 62 +/- 4.9), and CaM (450 +/- 18 vs 174 +/- 6.9) (microM pi/min/mg protein, control (0 microM betaine) vs 100 micromol/L betaine). Sorbitol (100 micromol/L) inhibited the Ca(2+)-ATPases by 41% (126 +/- 7.6 vs 74 +/- 4.4) and CaM by 42% (253 +/- 17.7 vs 147 +/- 10.3). Inositol (100 micromol/L) inhibited Na(+)/K(+)-ATPase strongest (37 +/- 1.9 vs 20 +/- 1.0; 47% inhibition) while it showed a lesser effect on the Ca(2+)-ATPases (136 +/- 6.8 vs 102 +/- 5.1; 25% inhibition). All osmolytes inhibited RBC membrane ATPases at concentrations above 50 micromol/L, which corresponds to high normal physiologic range for organic osmolytes in serum. Furthermore, the presence of osmolytes (250 micromol/L) decreased hypoosmotic stress induced hemolysis by 42%. Together these data indicate an important regulatory role of organic osmolytes on human RBC membrane ATPases and a protective function of osmolytes in RBCs against hypoosmotic stress. 相似文献