Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An RNA-directed DNA polymerase was purified from mouse spleen infected with leukaemia virus activated during N-methyl-N-nitroso urea- (MNU-) induced leukaemogenesis. The enzyme was isolated from the microsomal fraction and purified by successive chromatography of Sephadex G-200 and phosphocellulose. Estimation of molecular weight from the sedimentation rate of the purified enzyme in a sucrose gradient gave a value of 70,000. The enzyme had a pH optimum of 7.4, a KC1 optimum of 50 mmol/l, an Mn2+ optimum of 0.2 mmol/l, and a temperature optimum of 25 degrees C, when (rA)n . (dT) 10 was used as the template-primer. It preferred (rA)n . (dT)10 as the template-primer and transcribed (rC)n . (dG) 12 and (OMeC)n . (dG)12. A comparison of the properties of this DNA polymerase with the enzyme purified from murine type C retroviruses showed that the MNU-activated virus enzyme was both biochemically and biophysically indistinguishable from murine leukaemia virus DNA polymerases.
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PMID:Characterization of an RNA-directed DNA polymerase from mouse spleen infected with leukaemia virus activated during N-methyl-N-nitroso urea-induced leukaemogenesis. 617 78

Several new analogues of polyadenylic acid [(A)n], i.e. poly(2-fluoroadenylic acid) [(fl2A)n], poly(2-chloroadenylic acid [(cl2A)n], poly(2-bromoadenylic acid) [(br2A)n] and poly(2-iodoadenylic acid) [(io2A)n] have been synthesized and evaluated for their effects on the RNA-directed DNA polymerase (reverse transcriptase) activity of Moloney murine leukaemia virus. All (A)n analogues were found to be potent inhibitors of reverse transcriptase, the order of (decreasing) potency being (fl2A)n greater than (io2A)n greater than (br2A)n greater than (cl2A)n. For all four (A)n analogues the inhibition of reverse transcriptase was competitive with respect to the template-primer. (A)n . oligo(dT). The K1 values were 0.02 microgram/ml for (fl2A)n, 0.1 microgram/ml for (io2A)n, 0.5 microgram/ml for (br2A)n and 8 microgram/ml for (cl2A)n. With a Ki of 0.02 microgram/ml (approx. 0.04 microM), (fl2A)n can be considered as one of the most, if not the most, potent polynucleotide inhibitor of reverse transcriptase that has been described so far.
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PMID:Inhibition of murine leukaemia virus reverse transcriptase by 2-halogenated polyadenylic acids. 618 Jul 34

The 2'-substituted analog of poly(inosinic acid) ((I)n), poly(2'-fluoro-2'-deoxyinosinic acid) ((dIfl)n) served as an effective template for the RNA-directed DNA polymerase (reverse transcriptase) from Moloney murine leukemia virus. When assayed under the same conditions, the parent compound (I)n showed little, if any, template activity. In the presence of other templates, i.e. poly (2-O-methylcytidylic acid), (dIfl)n could also assume the role of primer for the reverse transcriptase reaction, whereas, again, (I)n failed to do so.
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PMID:Template activity of poly(2'-fluoro-2'-deoxyinosinic acid) for murine leukemia virus reverse transcriptase. 618 66

The quinoline U-78036 represents a new class of non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitors. The agent possesses excellent antiviral activity at nontoxic doses in HIV-1-infected lymphocytes grown in tissue culture. Enzymatic kinetic studies of the HIV-1 reverse transcriptase (RT)-catalyzed RNA-directed DNA polymerase function were carried out in order to determine whether the inhibitor interacts with the template-primer or deoxyribonucleotide triphosphate (dNTP) binding sites of the polymerase. The data were analyzed using steady-state or Briggs-Haldane kinetics assuming that the template-primer binds to the enzyme first followed by the dNTP and that the polymerase functions processively. The calculated rate constants are in agreement with this model. The results show that the inhibitor acts as a mixed to noncompetitive inhibitor with respect to both the template-primer and the dNTP binding sites of the enzyme. Hence, U-78036 inhibits the RNA-directed DNA polymerase activity of RT by interacting with a site distinct from the template-primer and dNTP binding sites. Moreover, the potency of U-78036 is dependent on the base composition of the template-primer. The equilibrium constants for various enzyme-substrate-inhibitor complexes were at least seven times lower for the poly(rC).(dG)10-catalyzed system than the one catalyzed by poly(rA).(dT)10. In addition, the inhibitor does not impair the DNA-dependent DNA polymerase activity and the RNase H function of HIV-1 RT nor does it inhibit the RNA-directed DNA polymerase activity of the HIV-2, avian myoblastoma virus, and murine leukemia virus RT enzymes.
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PMID:The quinoline U-78036 is a potent inhibitor of HIV-1 reverse transcriptase. 768 7

The UV inactivation of RNA-directed DNA polymerase activity of Rauscher leukemia virus was shown to be due to damage to the protein. The UV dose resulting in 37% survival of viral polymerase activity at 254 nm was 2.4 x 10(4) to 3.1 x 10(4) ergs/mm(2). The inactivation rate of p30, a major internal viral protein, was much slower.
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PMID:Effect of UV Light on RNA-Directed DNA Polymerase Activity of Murine Oncornaviruses. 1678 59


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