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1.
《Bioorganic & medicinal chemistry》2016,24(18):4444-4451
Nowadays, AT1 receptor (AT1R) antagonists (ARBs) constitute the one of the most prevalent classes of antihypertensive drugs that modulate the renin-angiotensin system (RAS). Their main uses include also treatment of diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. Towards this direction, our study has been focused on the discovery of novel agents bearing different scaffolds which may evolve as a new class of AT1 receptor antagonists. To fulfill this aim, a combination of computational approaches and biological assays were implemented. Particularly, a pharmacophore model was established and served as a 3D search query to screen the ChEMBL15 database. The reliability and accuracy of virtual screening results were improved by using molecular docking studies. In total, 4 compounds with completely diverse chemical scaffolds from potential ARBs, were picked and tested for their binding affinity to AT1 receptor. Results revealed high nanomolar to micromolar affinity (IC50) for all the compounds. Especially, compound 4 exhibited a binding affinity of 199 nM. Molecular dynamics simulations were utilized in an effort to provide a molecular basis of their binding to AT1R in accordance to their biological activities. 相似文献
2.
Early Inhibition of Acetylcholinesterase and Choline Acetyltransferase Activity in Herpes simplex Virus Type 1 Infection of PC12 Cells 总被引:1,自引:0,他引:1
Abstract: Early in the course of productive Herpes simplex virus type 1 (HSV-1) infection of PC12 cells, activities of both acetylcholinesterase (AChE) and choline acetyltransferase (CAT) fell. Studies using metabolic inhibitors and a temperature-sensitive mutant of the virus suggested that the decline in activities of both enzymes was associated with events occurring early in the replicative cycle related to expression of the immediate-early (α) group of viral polypeptides. HSV-1 gene products thus may alter specialized cell functions well before the production of viral progeny and initiation of cell lysis. The early clinical manifestations of nervous system viral infection may reflect focal metabolic disturbance rather than, or in addition to, simple cell death. 相似文献
3.
Leonard F. Liebes Howard Fleit Dorothea Zucker-Franklin Robert Silber 《Biochimica et Biophysica Acta (BBA)/General Subjects》1980,633(2):245-257
Tubulin has been purified from human blood and tonsil lymphocytes. Using gel filtration, the molecular weight of human lymphocyte tubulin was estimated to be 119 000. The proteins was shown to consist of two subunits, with molecular weights of 61 000 and 58 000 comparable to the α and β polypeptides of human brain tubulin. A partial identity reaction was observed between lymphocyte tubulin and human tubulin when tested by double immunodiffusion against a rabbit anti-human brain tubulin antibody. In the presence of GTP, the purified protein polymerized to form microtubules. Tubulin was localized to the cell's juxtacentriolar region by immunofluorescence and electron microscopy. When assayed by a colchicine-binding assay corrected for time decay, the binding affinity was 1.50 ± 0.86 · 106M?1 and a level in normal lymphocytes of 1.21 · 10?2 ± 0.79 g/g of soluble protein was determined. Since chronic lymphocytic leukemia lymphocytes have an anomalous capping behavior as well as an unusual susceptibility to colchicine toxicity, the properties and levels of tubulin were determined in these cells. Similar values were obtained for the level, decay rate, molecular weight, and Ka for colchicine as for normal lymphocytes. Chronic lymphocytic leukemia lymphocyte tubulin polymerized in a normal fashion. It thus appears that a decrease in the quantity or function of tubulin does not account for these anomalies in the chronic lymphocytic leukemia lymphocyte. 相似文献
4.
《Saudi Journal of Biological Sciences》2017,24(1):1-10
Uranium has been defined in material research engineering field as one of the most energetic radioactive elements in the entire Mendeleev periodic table. The manipulation of uranium needs higher theories and sophisticated apparatus even in nuclear energy extraction or in many other chemical applications. Above the nuclear exploitation level, the chemical conventional approaches used, require a higher temperature and pressure to control the destination of ionic form. However, it has been discovered later that at biological scale, the manipulation of this actinide is possible under friendly conditions. The review summarizes the relevant properties of uranium element and a brief characterization of nanoparticles, based on some structural techniques. These techniques reveal the common link between chemical approaches and biological assistance in nanoparticles. Also, those biological entities have been able to get it after reduction. Uranium is known for its ability to destroy ductile materials. So, if biological cell can really reduce uranium, then how does it work? 相似文献
5.
A. Benito E. Viaplana J.L. Corchero X. Carbonell A. Villaverde 《FEMS microbiology letters》1995,129(2-3):157-162
Abstract The 3D gene of foot-and-mouth disease virus encodes the viral RNA dependent RNA polymerase, also called virus infection associated (VIA) antigen, which is the most important serological marker of virus infection. This 3D gene from a serotype Cl virus has been cloned and overexpressed in Escherichia coli under the control of the strong lambda lytic promoters. The resulting 51 kDa recombinant protein has been shown to be immunoreactive with sera from infected animals. After induction of gene expression, an immediate and dramatic arrest of cell DNA synthesis occurs, similar to that produced by genotoxic doses of the drug mitomycin C. This effect does not occur during the production of either a truncated VIA antigen or other related and non-related viral proteins. The inhibition of DNA replication results in a subsequent induction of the host SOS DNA-repair response and in an increase of the mutation frequency in the surviving cells. 相似文献
6.
David A. Smith John L. Glover Laurace E. Townsend Diane E. Maupin 《In vitro cellular & developmental biology. Animal》1991,27(12):914-920
Summary Myocardial cell culture methods are now well established for animal and fetal human tissue. We present here a method for harvesting
and culturing adult human atrial myocardiocytes. Cells are obtained from fresh atrial tissue normally discarded after being
removed to cannulate the right atrium during open heart surgery. The atrial tissue is minced and then digested using collagenase.
The single cell suspension is initially cultured in serum-containing growth medium, then transferred to defined medium, selective
for myocardial cell growth. The cells are characterized by immunoperoxidase stains and transmission electron microscopy. The
cultured cells stain positive for myoglobin, whereas control cultured fibroblasts and endothelial cells do not. Electron microscopy
shows the presence of numerous myofibrils, Z-bodies, pleomorphic mitochondria, and secretory granules. The chronological age
of the donor was an important factor in culturing the adult tissue, the younger tissue correlated with a higher success rate.
This method provides a means for in vitro study of human adult myocardial cells and provides guidelines for appropriate atrial
tissue to use. 相似文献
7.
Vmw65, the Herpes Simplex Virus trans-activator of immediate-early genes, was expressed in insect cells using a recombinant baculovirus expression vector and partially purified. Insect cell-derived Vmw65 was shown to be indistinguishable from authentic Vmw65 present in purified HSV-1 virions based on electrophoretic mobility, immunoreactivity with a monoclonal antibody, and ability to interact with cellular factors to form a protein/DNA complex with oligonucleotides containing a TAATGARAT element.Abbreviations AcNPV
Autographica californica nuclear polyhedrosis virus
- HSV
Herpes Simplex Virus
- IE
Immediate Early
- moi
multiplicity of infection
- Sf9
Spodoptera frugiperda cells 相似文献
8.
Josée Harel Linda Duplessis Jeffrey S. Kahn Michael S. DuBow 《Archives of microbiology》1990,154(1):67-72
The 37,000 bp double-stranded DNA genome of bacteriophage Mu behaves as a plaque-forming transposable element of Escherichia coli. We have defined the cis-acting DNA sequences required in vivo for transposition and packaging of the viral genome by monitoring the transposition and maturation of Mu DNA-containing pSC101 and pBR322 plasmids with an induced helper Mu prophage to provide the trans-acting functions. We found that nucleotides 1 to 54 of the Mu left end define an essential domain for transposition, and that sequences between nucleotides 126 and 203, and between 203 and 1,699, define two auxiliary domains that stimulate transposition in vivo. At the right extremity, the essential sequences for transposition require not more than the first 62 base pairs (bp), although the presence of sequences between 63 and 117 bp from the right end increases the transposition frequency about 15-fold in our system. Finally, we have delineated the pac recognition site for DNA maturation to nucleotides 32 to 54 of the Mu left end which reside inside of the first transposase binding site (L1) located between nucleotides 1–30. Thus, the transposase binding site and packaging domains of bacteriophage Mu DNA can be separated into two well-defined regions which do not appear to overlap.Abbreviations
attL
attachment site left
-
attR
attachment site right
- bp
base pairs
- Kb
kilobase pair
- nt
nucleotide
- Pu
Purine
- Py
pyrimidine
- Tn
transposable element
State University of New York, Downstate Medical Center, Brooklyn, NY 11204 USA 相似文献
9.
Crispin J. Woolston Richard Barker Helen Gunn Margaret I. Boulton Philip M. Mullineaux 《Plant molecular biology》1988,11(1):35-43
Cloned DNA of the geminivirus wheat dwarf virus (WDV) was successfully used to infect seedling wheat plants. The clone was derived from circular double-stranded viral DNA isolated from naturally infected tissue. The initiation of infection was mediated by Agrobacterium tumefaciens using cloned dimeric WDV genomes in a binary Agrobacterium vector. The WDV DNA which comprised the infectious clone was sequenced and is compared with the published sequence of a Swedish isolate of the same virus. The results confirm that the single WDV genome component of 2.75 kb carries all the information necessary for production of viral symptoms, virus particles and viral double- and single-stranded DNA forms. 相似文献
10.
不同动物制备的抗血清对病毒抗原免疫反应的差异 总被引:1,自引:0,他引:1
血清学技术是病毒诊断、鉴定、分类及亲缘关系分析的重要手段。一般常用以制备抗病毒血清的动物是家兔,但也有采用其它动物的,如蛙、羊、豚鼠、鸡及小鼠等。本文比较了Balb/c小鼠、昆明种小鼠和新西兰大白兔对长叶车前花叶病毒上海分离株(RMVsh)和烟草花叶病毒普通株(TMVc)的免疫反应特征。 相似文献