Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4'-(9-Acridinylamino)methanesulphon-m-anisidide (AMSA) (NSC 141549), an acridine derivative with activity against a variety of laboratory tumors in vivo, is presently undergoing Phase 1 clinical evaluation. The interaction of AMSA with DNA and its effects on nucleic acid-polymerizing enzymes were examined in an attempt to define the site of cytotoxicity of AMSA. Binding of AMSA to DNA, as demonstrated by equilibrium dialysis and spectrophotometric methods, appears to be similar to other aminoacridines, in that two types of binding sites (type 1 and type 2) were observed. Fluorescence studies and thermal denaturation studies gave strong evidence that AMSA type 1 binding was by intercalation into DNA. The binding of AMSA to DNA was without marked base-pair specificity. Furthermore, the effect of AMSA on nucleic acid-polymerizing enzyme activities (mouse embryo DNA polymerase alpha, avian myeloblastosis virus reverse transcriptase, and Escherichia coli RNA polymerase) was studied. Inhibition of enzyme activity by AMSA appeared to be independent of DNA base sequence. The relatively high concentrations of AMSA required for inhibition of these enzymes as compared to the concentrations of AMSA necessary for cytotoxicity in vitro suggest that the interaction with DNA alone might not fully explain its antitumor activity.
...
PMID:Interaction of 4'-(9-acridinylamino)methanesulfon-m-anisidide with DNA and inhibition of oncornavirus reverse transcriptase and cellular nucleic acid polymerases. 7 12

During eight successive isologous passages of hepatoma induced in male C3HA mice by N-nitrosodiethylamine, no common features of tumor progression were observed, although both the mitotic pattern and ploidy differed from generation to generation. These additional cytologic criteria allowed the biochemical examination of material least changed due to tumor progression. Tumor nDNA's were characterized by greater actinomycin D (AD)- and acridine orange (AO)-binding abilities than were normal nDNA's; this could have resulted from a higher proportion of double-stranded regions in tumor DNA. Isolated tumor deoxyribonucleoprotein had both lower template activity in an RNA polymerase system and fewer AD- and AO-binding sites, when compared with the activity and sites from normal mouse liver. RNA-DNA hybridization data with the above-mentioned findings showed that in hepatoma, part of the nuclear genome was repressed. Also, RNA "new classes" appeared and a certain proportion of nuclear genes controlling mitochondrial protein biosynthesis were derepressed in tumor mitochondria. The hybridization of mitochondrial RNA (mtRNA) and DNA revealed new classes of pulse-labeled RNA's in in vitro-incubated liver mitochondria that were absent from intact cell organelles; the hybridization properties of in vivo- and in vitro-formed hepatoma mtRNA's were similar. Competition and hybridization experiments demonstrated that in tumor mitochondria in vivo, some new classes of RNA existed. Hepatoma mitochondrial mRNA had a higher metabolic stability than did normal mRNA.
...
PMID:Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice. 18 62

A homologous series of diacridines, as well as 9-amino acridine, were assayed for their ability to interfere with the synthesis of RNA (bands U-VI) by bacteriophage T7 DNA-dependent RNA polymerase transcribing T7 DNA in vitro; their action was compared to that of actinomycin D. It was found that, in contrast to actinomycin D which inhibits chain elongation, the acridines tested inhibited chain initiation only; no evidence for inhibition of chain elongation was noted. No clear-cut differentiation between single and double intercalators on the mechanism of inhibition of RNA synthesis could be determined, except that the latter are more potent inhibitors. However, it appears that diacridines connected with a diethyldiamine and a butyldiamine chain are less inhibitory to the synthesis of the RNA of Bands III and IV. The results furthermore indicate that the estimation of the number average molecular weight alone, without identification of the product RNA, is a potentially misleading method of determining the mode of action of these drugs.
...
PMID:The mechanism of inhibition of bacteriophage T7 RNA synthesis by acridines, diacridines and actinomycin D. 31 65

Acridine dyes inhibit the incorporation of 3H-thymidine and 3H-uridine in intact cells to the same extent as Actinomycin D. In contrast to Actinomycin D, RNA synthesis by DNA - dependent RNA polymerase in a cell-free system is inhibited at lo2 higher concentrations of acridine dyes, only. Possible differential effects on the cell membrane resulting in decreased intracellular pools of uridine and thymidine are discussed.
...
PMID:[The effect of actinomycin d, acridine dyes and related substances on the biosynthesis of nucleic acids in normal and leukemic white blood cells. Comparative investigation in intact cells and in a cell-free system (author's transl)]. 117 98

Guinea-pig and mouse liver chromatin responds to the partial hepatectomy by an increase in binding of a basic dye acridine orange (AO) and by a decrease of its stability to heat in thermal denaturation test in situ. Degree of the changes in AO chromatin binding is identical in the cells of different ploidy and proportional to their DNA content. Treatment of the preparations by 0.6 M NaCl solutions under conditions bringing about the selective removal of histone H1 from the cells produces in vitro changes in DNA properties taking place in cells in vivo in the course of their activation. The treatment of cells with 0.35 M NaCl solution results in the disappearance of changes occurring in the chromatin of activated cells whereas the properties of control cells remain unchanged. The data obtained are interpreted as a result of the removal of some non-histone regulatory proteins from the chromatin of activated cells that is accompanied by changes in the character of DNA-histone interaction. At the time of maximum increase of AO binding a significant intensification of endogenous RNA polymerase activity was found, the incorporation of [3H] UTP in the nucleolus being higher than that in the extranucleolar part of the nucleus. High ionic strength in the incubation medium (0.4 M (NH4)2SO4) results in drastic increase of radioactive label in the nucleus and in the disappearance of differences between activated and non-activated chromatin. It is concluded that the intensification of RNA synthesis under the influence of proliferative stimulus is more likely dependent on the additional opening of DNA-matrix than on the direct activation of the enzyme.
...
PMID:[Early changes in liver chromatin in response to partial hepatectomy]. 121 68

An in vitro T7 bacteriophage transcription system has been utilized in which the RNA was initiated to a specific length (defined by the absence of the appropriate nucleoside triphosphate). When the DNA-RNA-RNA polymerase ternary complex was exposed to nonsaturating levels of DNA-binding ligands (i.e., a small fractional occupancy at each site), and the RNA transcript then allowed to elongate in the presence of all four nucleoside triphosphates, there was a synchronous increase of RNA lengths up to sites occupied by ligands. A unique characteristic is that bacteriophage transcription was completely terminated at every ligand site, in contrast to bacterial RNA polymerases where "read-through" past drug sites occurs and results merely in a delay of transcription at each site due primarily to dissociation of drug from the DNA. Similar termination of transcription at each drug site was observed with T3 and SP6 RNA polymerases. The termination at drug sites in the bacteriophage system results in RNA of specific lengths which define the location of ligand sites, and the RNA concentration provides a measure of relative ligand occupancy at that site. Termination of transcription was observed with four drugs with relatively long DNA residence times (half-life greater than or equal to 300 s at 20 degrees C for nogalamycin, actinomycin, mithramycin, and echinomycin) but to a lesser extent with drugs of intermediate residence times [a bis(thiadaunomycin) and an acridine-tripyrrole, with half-lives of 230 and 7 s, respectively, at 20 degrees C]
...
PMID:Sequence-dependent termination of bacteriophage T7 transcription in vitro by DNA-binding drugs. 252 55

The purpose of this study was to examine effects of aphidicolin and alpha-amanitin on visualization of acridine orange (AO) binding to DNA in rat astrocytoma C6 cells and to discuss briefly the significance of AO chromatin interaction products. Aphidicolin inhibited DNA synthesis but percentage of AO positive cells was approximately 60% of that of the untreated control cells. alpha-Amanitin caused a slight inhibition of RNA synthesis and 3H-uridine incorporation in the treated cells was about 64% of that of the untreated cells, whereas a distinct decrease of the number of AO positive cell nuclei was observed. The results suggest that activity of RNA polymerase II and mRNA synthesis is mainly concerned in visualization of AO chromatin interaction products.
...
PMID:Effects of aphidicolin and alpha-amanitin on visualization of acridine orange binding to DNA in rat astrocytoma C6 cells. 258 4

Oligodeoxynucleotides covalently linked to an acridine derivative were targeted to part of the 3'-terminal sequence which is common to the eight RNAs of type A influenza viruses. The cytopathic effect of the virus on MDCK cells in culture was strongly decreased by a heptanucleotide covalently attached to the acridine ring. Control experiments using other oligonucleotide sequences showed that the effect was specific for the complementary sequence of the 3'-terminal region of the viral RNAs. The RNA transcriptase reaction of a type A virus was also selectively inhibited in vitro by the heptanucleotide-acridine conjugate. A type B influenza virus was used as a control. The common sequence at the 3' end of its eight viral RNAs is different from that of type A viruses. Three mismatches were expected with the heptanucleotide which was fully complementary to type A viral RNAs. This heptanucleotide had no effect on the cytopathic effect of a type B influenza virus. These results demonstrate that viral RNAs are specific targets for the oligonucleotide-acridine conjugate that inhibits the cytopathic effect of type A influenza viruses.
...
PMID:Selective inhibition of the cytopathic effect of type A influenza viruses by oligodeoxynucleotides covalently linked to an intercalating agent. 369 85

The purpose of this study was to examine the effects of actinomycin D on localization of acridine orange (AO) binding to DNA in rat astrocytoma C6 cells and to discuss briefly the significance of AO chromatin interaction products. Actinomycin D markedly inhibited 3H-uridine incorporation into RNA and the percentage of AO positive cells was reduced to approximately 40% of that of the untreated control cells, whereas no distinct decrease of 3H-thymidine incorporation was induced by actinomycin D. Electron microscopic radioautography combined with the AO ultracytochemistry revealed that silver grains indicating binding of 3H-actinomycin D are located mostly over the euchromatin portion near the segregated nucleolus and heterochromatin and that no or only a few AO chromatin complex was found in nuclei labeled heavily with 3H-actinomycin D. These results of the present study together with the results of the previous studies seem to indicate that AO might selectively bind to active or derepressed DNA template sites for DNA dependent RNA polymerase in the euchromatin portion of the cell nucleus.
...
PMID:Effects of actinomycin D on localization of acridine orange chromatin interaction complex in rat astrocytoma C6 cells. 371 93

Oligodeoxynucleotides have been covalently linked to a 9-aminoacridine derivative via their 3'-phosphate group. Specific complexes are formed with the complementary sequence of the oligonucleotide. The stability is strongly increased due to intercalation of the acridine derivative. Absorption, fluorescence, nuclear magnetic resonance and circular dichroism have been used to characterize complex formation. The stability of the complexes depends on the length of the linker between the acridine derivative and the 3'-phosphate group of the oligonucleotide. Oligonucleotides covalently linked to an intercalating agent can be used to selectively control gene expression. Transcription initiation can be blocked when such an oligonucleotide binds to the transcribed strand in the open complex formed by E. coli RNA polymerase with the bla promoter. With some oligonucleotides, non-specific effects on transcription can be detected, most probably due to binding of the modified oligonucleotide to RNA polymerase. Translation of the messenger RNA from gene 32 of phage T4 can be prevented by using an oligonucleotide complementary to the sequence upstream from the Shine-Dalgarno sequence. Inhibition of translation does not occur in the absence of the intercalating agent covalently linked to the oligonucleotide nor with oligonucleotides which do not have a target sequence on the mRNA.
...
PMID:Oligodeoxynucleotides covalently linked to intercalating agents: a new class of gene regulatory substances. 391 Jan 11


1 2 3 Next >>

---