Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new potent inhibitor of adenosine deaminase (co-vidarabine) was used in combination studies with adenine arabinoside (vidarabine, Vira-ATM) to protect this purine nucleoside from enzymatic deamination to the more weakly active metabolite, hypoxanthine arabinoside. Comparing the combination to vidarabine alone, a significant increase (10-fold) of the antiviral activity of the combined drugs was observed against herpes and vaccinia viruses in tissue culture and subcutaneously, against cranial herpesvirus infections in mice. Several other investigators have also recently reported several-fold enhancement of vidarabine activity by newly described deaminase inhibitors. They observed that plaque formation by several large DNA-containing viruses (herpes, vaccinia, varicella zoster) and an RNA-containing oncogenic virus was markedly prevented by the combination compared to vidarabine alone. In animals, enhanced protection (increased survivors) and/or highly significant increase in the life span of dying mice treated with the 2-drug combination, was also observed compared to vidarabine administered singly. These observations in animals clearly indicate that combination studies with vidarabine (Vira-ATM) and co-vidarabine (deaminase inhibitor) deserve serious consideration as future therapy for systemic virus infections in man including herpesvirus encephalitis.
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PMID:Effect of a novel adenosine deaminase inhibitor (co-vidarabine, co-V) upon the antiviral activity in vitro and in vivo of vidarabine (Vira-Atm) for DNA virus replication. 21 90

Certain D-arabinosyl nucleosides, notably arabinosyl cytosine (araC) and arabinosyl adenine (araA), are useful in the treatment of certain leukemias and some DNA virus infections, respectively. The compounds are lethal to animal cells and some bacteria. Despite extensive deamination, the parent nucleosides are transported within sensitive cells and phosphorylated to the mono-, di- and triphosphates. AraCTP and araATP are good specific competitive inhibitors of tumor cell of virus-induced DNA polymerases, competing with dCTP and dATP respectively. In addition to markedly inhibiting DNA synthesis, the aranucleotides enter newly formed DNA in internucleotide linkage. Sensitivity to the nucleosides appears to correlate with the relative ratio of formation of the triphosphate via a nucleoside kinase to degradation of the nucleoside via a nucleoside deaminase. Inhibition of the deaminase increases formation of the aranucleoside triphosphate in leukemic or virus-infected cells and markedly increases the toxicity of the nucleosides. Combinations of inhibitors of the deaminases and of the aranucleoside are being explored in clinical situations. In addition, the slow penetration of aranucleotides into cells has been observed and some of these 5'-phosphates are useful antiviral agents, e.g., against herpes virus in herpetic kiratitis.
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PMID:The mechanisms of lethal action of arabinosyl cytosine (araC) and arabinosyl adenine (araA). 32 34

Certain D-arabinosyl nucleosides, notably D-arabinosyl cytosine (araC) and D-arabinosyl adenine (araA), are useful in the treatment of certain leukemias and some DNA virus infections, respectively. The compounds are lethal to animal cells and some bacteria. Despite extensive deamination, the parent nucleosides are transported within sensitive cells and phosphorylated to the mono-, di- and triphosphates. AraCTP and araATP are good specific competitive inhibitors of tumor cell or virus-induced DNA polymerases, competing with dCTP and dATP, respectively. In addition to markedly inhibiting DNA synthesis, the aranucleotides enter newly formed DNA in internucleotide linkage. Sensitivity to the nucleosides appears to correlate with the relative ratio of formation of the triphosphate via a nucleoside kinase to degradation of the nucleoside via a nucleoside deaminase. Inhibition of the deaminase increases formation of the aranucleoside triphosphate in leukemic or virus-infected cells and markedly increases the toxicity of the nucleosides. Combinations of inhibitors of the deaminases and of the arnaucleoside are being explored in clinical situations. In addition, the slow penetration of aranucleotides into cells has been observed and some of these 5'-phosphates are useful antiviral agents, e.g. against herpes virus in herpetic keratitis.
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PMID:The lethality of aranucleotides. 82 87

The activities of dCMP deaminase and DNA polymerase I increased twofold and fivefold in BHK-21/C13 cells after infection by the virus of herpes simplex. The increases were greatly diminished, and under certain conditions prevented, by inclusion of actinomycin D or cycloheximide in the cell-virus system during the infective cycle. The dCMP deaminase purified from infected cells harvested 8h after infection differed from the deaminase purified from non-infected cells inasmuch as (a) it was more resistant to heating at 37 degrees C; (b) the substrate (dCMP) concentration at half-maximum velocity was lower; (c) maximum activation was achieved by a lower concentration of dCTP; (d) it was more resistant to inhibition by dTTP; and (e) it behaved differently when assayed in the presence of a herpes-virus-specific antiserum. The DNA polymerase activity in the infected cells was markedly decreased in the presence of the herpes-virus-specific antiserum.
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PMID:Deoxycytidylate deaminase evidence for a new enzyme in cells infected by the virus of herpes simplex. 437 45