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1.
Judith M. Clarkson David L. Mitchell 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,740(4):355-361
The effect on DNA repair of several inhibitors of DNA synthesis has been investigated in CHO cells. Three assays were employed following ultraviolet irradiation of G1 cells: unscheduled DNA synthesis, removal of antibody binding sites and alkaline elution. Cytosine arabinoside and aphidicolin were found to reduce unscheduled DNA synthesis in a dose-dependent manner without affecting the removal of antibody-binding sites. Strand rejoining was also inhibited. These results are consistent with the hypothesis that inhibition is due to premature chain termination during repair synthesis some time after excision of the lesion. Conversely, inhibition of unscheduled DNA synthesis by novobiocin is paralleled by inhibition of excision of the lesion. However, no inhibition of incision was apparent. Since nalidixic acid, an inhibitor of topoisomerase II, did not inhibit excision, it is unlikely that the primary site of action of novobiocin is this topoisomerase. The possibility that a second topoisomerase and/or a polymerase are affected is discussed in the light of previously published data. 相似文献
2.
The effect of gyrase inhibitors and cyclic AMP on induction and glucose repression of the 6-hydroxy-nicotine oxidases in Arthrobacter oxidans 总被引:1,自引:0,他引:1
The induction by d,l-nicotine of the enantiozymes 6-hydroxy-L-nicotine oxidase and 6-hydroxy-D-nicotine oxidase in Archrobacter oxidans was differently affected by the inhibitors of Escherichia coli gyrase, novobiocin and nalidixic acid. These compounds inhibited 6-hydroxy-L-nicotine oxidase induction slightly, but led to an increase in the level of 6-hydroxy-D-nicotine oxidase activity. Furthermore, the specific repression by glucose of 6-hydroxy-D-nicotine oxidase synthesis was not abolished by the addition of cAMP but by that of novobiocin.Abbreviations 6-HDNO
6-hydroxy-D-nicotine oxidase
- 6-HLNO
6-hydroxy-L-nicotine oxidase
- cAMP
cyclic 3,5-adenosine monophosphate
- Enzymes
Adenylate cyclase
- ATP
pyrophosphate-lyase (cyclizing) (EC 4.6.1.1)
- cAMP-phosphodiesterase
3:5-cyclic-nucleotide 5-nucleotido-hydrolase (EC 3.1.4.17)
- DNA gyrase
DNA topoisomerase II (EC 5.99)
- DNA polymerase
deoxynucleosidetriphosphate: DNA desoxynucleotidyl-transferase (EC 2.7.7.7)
- 6-hydroxy-L-nicotine oxidase
6-hydroxy-L-nicotine: oxygen oxidoreductase (EC 1.5.3.5)
- 6-hydroxy-D-nicotine oxidase
6-hydroxy-D-nicotine: oxygen oxidoreductase (EC 1.5.3.6)
- -lactamase
penicillin amido--lactamhydrolase (EC 3.5.2.6)
- nicotine dehydrogenase
nicotine: (acceptor)6-oxidoreductase (hydroxylating) (EC 1.5.99.4) 相似文献
3.
Matts RL Brandt GE Lu Y Dixit A Mollapour M Wang S Donnelly AC Neckers L Verkhivker G Blagg BS 《Bioorganic & medicinal chemistry》2011,19(1):684-692
Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA. 相似文献
4.
Chlamydomonas is an unicellular green alga that contains one cup-shaped chloroplast with about 60 copies of cpDNA. Chloroplasts (cp) multiply
in the cytoplasm of the plant cell by binary division, with multiple copies of cpDNA transmitted and maintained in successive
generations. The effect of cpDNA copy number on cell proliferation and aging was investigated using a C. reinhardtii moc mutant, which has an undispersed cp-nucleoid and unequal segregation of cpDNA during cell division. When the mother cell
divided into four daughters, one moc daughter cell chloroplast contained about 60 copies of cpDNA, and the chloroplasts in the three other daughter cells contained
the 4–7 copies of cpDNA. In liquid medium, the number of moc cells at the period of stationary phase was about one-third that of the wild type. To observe the process of proliferation
and aging in the mother cell, we used solid medium. Three out of four moc cell spores were preferentially degenerated 60 days after cell transfer. To confirm this, wild-type and moc mother cells containing four daughter cells were treated with novobiocin to inhibit cpDNA replication. Cell degeneration
increased only in the moc strain following novobiocin introduction. In total, our results suggest that cells possessing smaller amounts of cpDNA degenerate
and age more rapidly.
Received 7 September 2000/ Accepted in revised form 14 February 2001 相似文献
5.
6.
《Bioorganic & medicinal chemistry letters》2014,24(15):3633-3637
Hsp90 represents a promising target for the development of both anti-cancer and neuroprotective agents. Structure–activity relationship studies on novobiocin and novobiocin analogues, led to the development of KU-32 and recently, KU-596, as lead compounds for the potential treatment of neurodegenerative diseases. Similar to KU-32, we have demonstrated that upon replacement of the acetamide side chain present in KU-32 with a benzamide, this neuroprotective agent was transformed into a scaffold that manifests anti-proliferative activity. To assess structure–activity relationships for this new scaffold, a library of benzamide-containing novologues was prepared and evaluated against two breast cancer cell lines. Compound 14a manifested the most potent anti-proliferative activity from these studies and induced Hsp90-dependent client protein degradation in a concentration-dependent manner. 相似文献
7.
Leah K. Forsberg Weiya Liu Jeffrey Holzbeierlein Brian S.J. Blagg 《Bioorganic & medicinal chemistry letters》2017,27(18):4514-4519
Heat Shock Protein 90 (Hsp90) is a molecular chaperone under clinical investigation for the treatment of neurodegenerative diseases and cancer. Neuroprotective Hsp90 C-terminal inhibitors (novologues) contain a biaryl ring system, and include KU-596, which was modified and investigated for potential anti-cancer activity. Incorporation of a benzamide group onto the biaryl novologues in lieu of the acetamide yielded compounds that manifest anti-cancer activity. Further exploration of the central phenyl ring led to compounds with enhanced anti-proliferative activity. The design, synthesis, and evaluation of these new analogs against breast and prostate cancer cell lines is reported herein, where it was found that 8b and 10 manifest potent anti-proliferative activity and a robust degradation of Hsp90 client-dependent proteins. 相似文献
8.
Aman Gupta Vanashika Sharma Ashish Kumar Tewari Vipul SurenderKumar Gulshan Wadhwa Ashwani Mathur Sanjeev Kumar Sharma Chakresh Kumar Jain 《Bioinformation》2013,9(3):116-120
Pseudomonas aeruginosa is an opportunistic bacterium known for causing chronic infections in cystic fibrosis and chronic obstructive
pulmonary disease (COPD) patients. Recently, several drug targets in Pseudomonas aeruginosa PAO1 have been reported using
network biology approaches on the basis of essentiality and topology and further ranked on network measures viz. degree and
centrality. Till date no drug/ligand molecule has been reported against this targets.In our work we have identified the ligand
/drug molecules, through Orthologous gene mapping against Bacillus subtilis subsp. subtilis str. 168 and performed modelling and
docking analysis. From the predicted drug targets in PA PAO1, we selected those drug targets which show statistically significant
orthology with a model organism and whose orthologs are present in all the selected drug targets of PA PAO1.Modeling of their
structure has been done using I-Tasser web server. Orthologous gene mapping has been performed using Cluster of Orthologs
(COGs) and based on orthology; drugs available for Bacillus sp. have been docked with PA PAO1 protein drug targets using
MoleGro virtual docker version 4.0.2.Orthologous gene for PA3168 gyrA is BS gyrAfound in Bacillus subtilis subsp. subtilis str. 168.
The drugs cited for Bacillus sp. have been docked with PA genes and energy analyses have been made. Based on Orthologous gene
mapping andin-silico studies, Nalidixic acid is reported as an effective drug against PA3168 gyrA for the treatment of CF and
COPD. 相似文献
9.
本文评价了所选用的DNA修复抑制剂对人类巨细胞病毒(HCMV)诱发外周血淋巴细胞(PBLs)染色体畸变频率的影响。以拓扑酶Ⅰ的一种抑制剂——喜树碱(0.05—0.3μg/m1)处理HCMV感染的人类PBLs30小时,结果导致HCMV诱发的染色体损伤频率显著的协同性增加(P<0.O1)。另一方面以ADP核糖聚合酶的一种抑制剂——3—氨基苯酰胺(3—AB)(3—30μg/ml),或者拓扑酶Ⅱ的一种抑制剂——新霉素(3—30μg/ml)处理HCMV感染的PBLs30时小,染色体损伤频率未见明显增加。在喜树碱处理的HCMV感染细胞中,染色单体型断裂包括染色体交换是染色体畸变的主要类型,这提示HCMV感染与单链NDA断裂有关,这些发现还提示,HCMV感染不会造成通过3-AB或新霉素敏感途径修复的直接DNA损伤。 相似文献
10.
Abstract During growth of Streptomyces niveus wild-type in the novobiocin production medium CDM the resistance of mycelia to novobiocin rises from about 25 μg/ml to over 200 μg/ml. ( S. lividans , a novobiocin-sensitive strain, is resistant to approx. 10 μg/ml novobiocin.) The initial period of low level resistance extends from the time of inoculation of the culture until approx. 70 h when the culture is still in the growth phase. High level resistance is initiated before the start of novobiocin production and rises rapidly to a maximum level beyond the end of the growth phase. The rise in pH of the unbuffered CDM medium which occurs during S. niveus fermentation was shown not to be the cause of the change in novobiocin resistance. However, mycelia-free CDM from S. niveus cultures expressing high level novobiocin resistance was shown to contain a factor which induced high level novobiocin resistance in germinating S. niveus spores. Kinetic studies revealed that the inducer first appears in the culture medium before the switch to high level resistance begins and reaches its highest concentration before resistance reaches its maximum level. 相似文献