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

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of various new anthracycline antibiotics on DNA and RNA synthesis were studied using DNA polymerase I (EC 2.7.7.7), RNA polymerase (EC 2.7.7.6) obtained from Escherichia coli and reverse transcriptase obtained from avian myeloblastosis virus. Aclacinomycin A, its analogues, baumycins A1 and A2, adriamycin and daunomycin showed potent inhibitory effects on these polymerases, with calf thymus DNA as template, with IC50 values of 10-30 microM. With poly(rA) x d(pT)10 as template for reverse transcriptase, aclacinomycin A and daunomycin showed IC50 values higher than 500 microM. Baumycins B1, B2, C1, and C2 showed high IC50 values on three polymerases. Addition of excess template DNA to the reaction mixture reversed the inhibitory effect of anthracyclines. Addition of calf thymus DNA to anthracyclines caused a bathochromic and hypochromic change in the visible spectrum. Apparent binding constant for aclacinomycin A, its analogues, and adriamycin were in the range of (1-2) X 10(6) M-1. Aclacinomycin A and adriamycin also bind to heat denatured DNA, but not strongly to yeast RNA. From these results, the structure-activity relationships of new anthracyclines on DNA binding and polymerase reactions are discussed.
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PMID:Interaction of new anthracycline antibiotics with DNA. Effects on nucleic acid synthesis and binding to DNA. 618 17

Protoberberine alkaloids such as palmatine (I), 13-methylpalmatine iodide (II), 2,3-methylenedioxy-10,11-dimethoxy-13-methylprotoberberine iodide (III), 2,3-methylenedioxy-9,10-dimethoxy-13-methylprotoberberine chloride (IV), and berberine (V) showed inhibition of reverse transcriptase activity of RNA tumor viruses in the presence of polyriboadenylic acid-oligodeoxythymidylic acid (VI), polydeoxyadenylic acid-oligodeoxythymidylic acid (VII), activated calf thymus deoxyribonucleic acid (IX), and 70S ribonucleic acid (X), but not in the presence of polyribocytidylic acid-oligodeoxyguanylic acid (VIII). These results indicated that the alkaloids caused inhibition of the enzyme activity by interacting with the template primer, particularly of the adenine-thymine base pair. Furthermore, the alkaloids competed with the template primer-binding site of the enzyme. The time course inhibition indicated that the alkaloids stopped the DNA synthesis instantly when added after the initiation of polymerization processes. Inhibition of reverse transcriptase activity was correlated with the structure and antileukemic activity of the protoberberine alkaloids.
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PMID:Enzyme inhibition VI: Inhibition of reverse transcriptase activity by protoberberine alkaloids and structure-activity relationships. 619 Oct 21

Turkeys inoculated at 5 weeks of age with lymphoproliferative disease (LPD) virus developed typical lesions in the spleen, thymus, and pancreas. The in vitro blastogenic response of peripheral blood lymphocytes to the mitogens phytohemagglutinin and concanavalin A was drastically (up to 90%) suppressed in the inoculated turkeys 1 to 4 weeks postinoculation compared with uninoculated controls, and even at 11 weeks the response was about 50% inhibited. A lethal (about LD33) dose of antihelminthic drug niridazole, 100 mg/kg given each day for 3 days to 4-week-old turkeys, caused a transient inhibition of the blastogenic response within 32 days of treatment, which was less pronounced than that observed in turkeys inoculated with LPD virus, whether pretreated with niridazole or not. Virus-associated reverse transcriptase activity in the plasma was significantly higher in the turkeys pretreated with niridazole, and LPD lesions developed to the same extent in the untreated and treated groups, as determined 9 weeks post virus inoculation. A sublethal dose of niridazole, 50 mg/kg given each day for 4 days, did not suppress the blastogenic response to mitogens at any time determined (starting 10 days post-treatment) and did not affect the pathogenesis of LPD and the viremia. Body weights were significantly decreased by virus infection and by treatment with lethal doses of niridazole.
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PMID:Effect of lymphoproliferative disease virus and of niridazole on the in vitro blastogenic response of peripheral blood lymphocytes of turkeys. 619 55

The diterpene ester promoter of mouse skin tumors, 12-O-tetradecanoylphorbol-13-acetate (TPA), efficiently induces Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase) activity in the EBV-producing lymphoblastoid cell line, P3HR-1. With the use of intervent dilution chromatography followed by sequential DEAE-cellulose and phosphocellulose column chromatography, the virus-associated enzyme has been isolated and purified 300-fold. The partially purified EBV DNA polymerase activity could be distinguished from cellular polymerases by its activation with salt and its degree of sensitivity to N-ethylmaleimide and phosphonoacetic acid. The enzyme showed maximum activity for copying activated calf thymus DNA in the presence of 100 mM ammonium sulfate. In the absence of salt, the enzyme utilized with high efficiency deoxyoligomer-homopolymer templates, but failed to copy poly(rA) . oligo(dT)10 and oligo(dT)10, showing that the enzyme had properties distinct from DNA polymerase gamma, reverse transcriptase, and terminal deoxynucleotidyltransferase. The partially purified enzyme is strongly inhibited by acyclovir triphosphate and thus has properties similar to herpes simplex virus DNA polymerase.
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PMID:Induction of Epstein-Barr virus-associated DNA polymerase by 12-O-tetradecanoylphorbol-13-acetate. Purification and characterization. 624 99

Inhibitors of bacterial DNA gyrase and eukaryotic DNA topoisomerase (novobiocin and nalidixic acid) were investigated with respect to their effect on the activity of RNA-dependent DNA polymerases from murine and avian retroviruses. Purified RNA-dependent DNA polymerase from AKR virus was inhibited more than 90% by 0.3 mg/ml and almost completely by 1 mg/ml of the drugs when poly(A) X oligo(dT)12-18 was used as a template-primer. In contrast to the enzyme from AKR virus, purified enzyme from avian myeloblastosis virus was less sensitive, i.e. nearly 50% activity remained even in the presence of 1 mg/ml of the drugs with the same template-primer. RNA-dependent DNA polymerase activity in AKR virus particles was inhibited, but was resistant to low concentrations of the drugs. The inhibition was not due to specific interaction between drugs and the template-primer or labelled precursor, since RNA-dependent DNA polymerase was inhibited by the drugs with activated calf thymus DNA or poly(C) X oligo(dG)12-18 as the template. Endogenous DNA synthesis by AKR virus particles was inhibited by novobiocin to the same extent.
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PMID:Inhibition of retrovirus RNA-dependent DNA polymerase by novobiocin and nalidixic acid. 631 59

1. Thymosin alpha 1 precursor [3H]cDNA-cellulose synthesis was carried out by reverse transcription with RNA-dependent DNA polymerase from avian myeloblastosis virus using oligo(dT)-bound to cellulose as a primer. 2. Unlabelled thymosin alpha 1 precursor cDNA-cellulose was synthetized in a preparative scale to be used in affinity chromatography. 3. Poly(A)-mRNA from calf thymus was subjected to cDNA-cellulose affinity chromatography and an active messenger obtained in a yield of 3% respect to the total thymus poly(A)-mRNA chromatographied. 3. The analysis of the translation products of the purified mRNA have shown it as the thymosin alpha 1 precursor messenger.
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PMID:Synthesis of thymosin alpha 1 precursor cDNA and purification of active mRNA by affinity chromatography. 640 38

Specific inhibitors and anti-DNA polymerase alpha IgG have been utilized to probe for similarities between cytoplasmic rat hepatic glucocorticoid receptors and DNA polymerase alpha [DNA nucleotidyltransferase (DNA-directed), EC 2.7.7.7]. Rifamycin AF/013, an inhibitor of RNA and DNA polymerase activities, significantly inhibited the binding of activated [6,7-3H]-triamcinolone acetonide (TA) receptor complexes to DNA-cellulose. beta-Lapachone, an inhibitor of DNA polymerase alpha and reverse transcriptase activities, inhibited the specific binding of [6,7-3H]TA when preincubated with unbound receptors. Aphidicolin, another DNA polymerase alpha inhibitor, failed to inhibit any of the glucocorticoid-receptor functions tested. Two specific anti-DNA polymerase alpha IgGs interfered with glucocorticoid receptor functions as measured by their ability to inhibit the binding of [6,7-3H]TA to unbound receptors (85% maximal inhibition) and, to a lesser extent, to inhibit the binding of activated [6,7-3H]TA receptor complexes to DNA-cellulose (50% maximal inhibition). The anti-DNA polymerase alpha IgG and beta-lapachone failed to affect the binding of tritiated estradiol, progesterone, or 5 alpha-dihydrotestosterone to their receptors in appropriate rat target tissues or the binding of [1,2-3H]hydrocortisone to serum transcortin. The most obvious interpretation of these data is that cytoplasmic glucocorticoid receptors and DNA polymerase alpha share antigenic determinants. An alternative interpretation is that the polyclonal anti-DNA polymerase alpha antibody contains IgG molecules raised against calf thymus cytoplasmic activated glucocorticoid-receptor complexes that copurified with DNA polymerase alpha used as the antigen. Taken collectively, however, the antibody and inhibitor data suggest a relationship between DNA polymerase alpha and the glucocorticoid receptor.
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PMID:Correlations between the activities of DNA polymerase alpha and the glucocorticoid receptor. 681 51

9-[2-(phosphonomethylcarbonylamino)ethyl]adenine, 9-[(2-phosphonoethyl)aminocarbonylmethyl]adenine, 9-[2-[(2-phosphonoethyl)carbonylamino]ethyl]adenine, and their diphosphates were synthesized. All three diphosphates were shown to incorporate into the 3'-terminus of the DNA chain during the synthesis of the avian myeloblastosis virus catalyzed by reverse transcriptase. However, they do not serve as substrates for DNA polymerase alpha from human placenta, polymerase beta from calf thymus, or terminal deoxynucleotidyl transferase from calf thymus.
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PMID:[Synthesis and some biochemical properties of phosphonyl acyclic analogs of 2'-deoxyadenosine nucleotides]. 748 70

Gene rearrangement during the ontogeny of T- and B-cells generates an enormous repertoire of T-cell receptor (TCR) and immunoglobulin (Ig) genes. Because of the error-prone nature of this rearrangement process, two-thirds of rearranged TCR and Ig genes are expected to be out-of-frame and thus contain premature terminations codons (ptcs). We performed sequence analysis of reverse transcriptase-polymerase chain reaction products from fetal and adult thymus and found that newly transcribed TCR-beta pre-mRNAs (intron-bearing) are frequently derived from ptc-bearing genes but such transcripts rarely accumulate as mature (fully spliced) TCR-beta transcripts. Transfection studies in the SL12.4 T-cell line showed that the presence of a ptc in any of several TCR-beta exons triggered a decrease in mRNA levels. Ptc-bearing TCR-beta transcripts were selectively depressed in levels in a cell clone that contained both an in-frame and an out-of-frame gene, thus demonstrating the allelic specificity of this down-regulatory response. Protein synthesis inhibitors with different mechanism of action (anisomysin, cycloheximide, emetine, pactamycin, puromycin, and polio virus) all reversed the down-regulatory response. Ptc-bearing transcripts were induced within 0.5 h after cycloheximide treatment. The reversal by protein synthesis inhibitors was not restricted to lymphoid cells, as shown with TCR-beta and beta-globin constructs transfected in HeLa cells. Collectively, the data suggest that the ptc-mediated mRNA decay pathway requires an unstable protein, a ribosome, or a ribosome-like entity. Protein synthesis inhibitors may be useful tools toward elucidating the molecular mechanism of ptc-mediated mRNA decay, an enigmatic response that can occur in the nuclear fraction of mammalian cells.
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PMID:A regulatory mechanism that detects premature nonsense codons in T-cell receptor transcripts in vivo is reversed by protein synthesis inhibitors in vitro. 749 32

The reverse transcriptase (RT) inhibition and the specificity of 15 aminonaphthalenesulfonic acid derivatives were examined with RT of a simian immunodeficiency virus derived from an African green monkey (SIVagmTYO-7). The two compounds with the strongest RT inhibition (NF415) or the highest specificity (NF345), together with suramin, were evaluated against polymerase alpha-primase complex from calf thymus. We have also compared the kinetics of inhibition of the viral and the cellular polymerase by these three compounds. While RT inhibition followed a mixed competitive and non-competitive mechanism, inhibition of the DNA polymerase alpha was competitive for suramin and non-competitive for NF415 and NF345. Certain structural characteristics appeared to be common for specific RT inhibitors.
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PMID:Chemical modifications of aminonaphthalenesulfonic acid derivatives increase effectivity and specificity of reverse transcriptase inhibition and change mode of action of reverse transcriptase and DNA polymerase alpha inhibition. 750 9


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