Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the fractionation of various enzymes concerned with DNA synthesis from the postmicrosomal supernatant fraction of various tissues, DNA polymerace [EC 2.7.7.7], thymidine kinase [EC 2.7.1.75], dTMP kinase [EC 2.7.4.9], deoxycytidine kinase [EC 2.7.1.74], and deoxycytidine monophosphokinase (dCMP kinase) [EC 2.7.4.14] were found in the pellet fraction of postmicrosomal supernatant. Further, the uridine kinase [EC 2.7.1.48] and aspartate transcarbamylase [EC 2.1.3.2] activities of postmicrosomal supernatant from various tissues were also present in this pellet fraction. The activities of DNA polymerase, thymidine kinase, uridine kinase, and aspartate transcarbamylase from normal and regenerating rat liver, and Yoshida sarcoma were higher in the pellet fraction than in the supernatant. On the other hand, the activities of dTMP kinase, dCMP kinase, and orotidine-5'-phosphate decarboxylase [EC 4.1.1.23] were lower in the pellet fraction than in the supernatant. The pellet fractions of regenerating rat liver and Yoshida sarcoma showed a remarkable incorporation of various precursors (thymidine, dTMP, deoxycytidine, and dCMP) into DNA in the presence of a suitable DNA template, ATP and all four deoxynucleoside 5'-triphosphates for DNA synthesis. Normal adult rat liver catalyzed a much smaller incorporation of all these precursors, except for dCMP.
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PMID:Intracellular distribution of various enzymes concerned with DNA synthesis from normal and regenerating rat liver, and Yoshida sarcoma. 113 86

Bisbrusatolyl malonate, which was shown previously to be active against P-388 lymphocytic leukemia cell growth, was investigated for inhibitory effects on nucleic acid and protein synthesis. DNA and RNA synthesis as well as protein synthesis were markedly inhibited at 10,25, and 50 mu mole final concentrations in vitro. The major sites of inhibition of nucleic acid synthesis appeared to be DNA polymerase, messenger and transfer RNA polymerases, orotidine-5'-monophosphate decarboxylase, phosphoribosyl pyrophosphate amino transferase, and dihydrofolate reductase. Moderate inhibition of nucleotide kinase activities and oxidative phosphorylation processes occurred after drug treatment. Cyclic adenosine monophosphate levels were reduced. Protein synthesis was inhibited during the elongation step of peptide synthesis. The data suggested that bisbrusatolyl malonate interfered with the peptide bond formation. However, the ongoing polypeptide synthesis must be completed before the drug can bind to the ribosome effectively.
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PMID:Antitumor agents XLVII: The effects of bisbrusatolyl malonate on P-388 lymphocytic leukemia cell metabolism. 627 24

Molephantinin, a germacranolide, has previously been shown to possess antineoplastic activity in rodents. The principle effect of molephantinin on Ehrlich ascites carcinoma cells was to depress DNA and protein synthesis both in vivo and in vitro. DNA synthesis was inhibited at the following sites: DNA polymerase, purine synthesis specifically at inosinic acid dehydrogenase and to a lesser degree at dihydrofolate reductase, pyrimidine synthesis at orotidine monophosphate decarboxylase, thymidine kinase, histone phosphorylation, and oxidative phosphorylation processes. The protein synthesis inhibition pattern resembled more an initiation inhibitor as opposed to an elongation inhibitor.
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PMID:Antitumor agents LII: The effects of molephantinin on nucleic acid and protein synthesis of Ehrlich ascites cells. 709 35

The era of antiviral chemotherapy started more than 50 years with the findings by Domagk and his colleagues that thiosemicarbazones showed activity against vaccinia virus. One of the derivatives, methisazone, was even investigated in the prophylaxis of smallpox. With the successful implementation of the smallpox vaccine, the use of methisazone was not further pursued. Should there be a threat of smallpox or other poxvirus infections, that could not be immediately controlled by vaccination, a therapeutic intervention could be envisaged based on several therapeutic strategies targeted at such cellular enzymes as IMP dehydrogenase, SAH hydrolase, OMP decarboxylase and CTP synthetase, as well as viral enzymes such as the DNA polymerase. Most advanced as a therapeutic or early prophylactic modality to tackle poxvirus infection is cidofovir, which was found active (i) in vitro against all poxviruses studied so far; (ii) in vivo, against vaccinia and cowpox virus infections in experimental animal models; as well as (iii) some human poxvirus infections, such as molluscum contagiosum. In case of an inadvertent poxvirus epidemic, antiviral therapy (i.e. with cidofovir) will offer the possibility to provide short-term prophylaxis, or therapy. Cidofovir should also allow to treat severe complications of vaccination as may happen in for example immunosuppressed patients.
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PMID:Therapy and short-term prophylaxis of poxvirus infections: historical background and perspectives. 1261