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)

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; erythro-9-[3-(hydroxynonyl)]adenine), a reversible inhibitor of adenosine deaminase, significantly inhibits replication of herpes simplex virus (HSV), whereas the more active inhibitor of the deaminase, 2'-deoxycoformycin, does not. At 10 micron EHNA, which does not affect viability, growth, or DNA synthesis of uninfected HeLa cells, production of HSV and HSV-specific DNA is inhibited 75-90% and 60%, respectively. HSV multiplies normally in cells pretreated with EHNA and washed to remove this inhibitor. EHNA (10 micron) also markedly potentiates the toxicity of adenine arabinonucleoside and of cordycepin (3'-deoxyadenosine) against HeLa cells and against the production of HSV in those cells. Cordycepin alone (10 micron) does not inhibit HSV replication whereas in combination with 10 micron EHNA there is a greater than 99% inhibition of virus production. Under these conditions, RNA synthesis is inhibited by more than 80% whereas protein and DNA synthesis are inhibited to a lesser extent; in this system, virtually all of the DNA synthesis in infected cells is that of host DNA. Thus, EHNA appears to affect the synthesis of HSV DNA specifically in two different ways, depending on whether it is used alone or in the presence of cordycepin.
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PMID:Erythro-9-(2-hydroxy-3-nonyl)adenine as a specific inhibitor of herpes simplex virus replication in the presence and absence of adenosine analogues. 21 93

The nucleoside analog 3'-deoxyadenosine (cordycepin) rapidly collapses the intermediate filaments into juxtanuclear caps in interphase fibroblasts and keratinocytes. A minimum of 80 micrograms/ml cordycepin or 20 micrograms/ml cordycepin in combination with 2 micrograms/ml of the deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenosine (EHNA) to inhibit its degradation is required to see these effects. This is the same concentration required for cordycepin to arrest cells at the onset of mitosis and depolymerize the microtubules to small asters. Cordycepin enters the cells rapidly and is phosphorylated to 3'-dATP with a concomitant drop in ATP levels. However, the direct reduction of ATP levels does not mimic the same rapid effects of cordycepin on either the intermediate filaments or microtubules. In addition, similar effects are not produced by a variety of other adenosine analogs with alterations in the 2'- and 3'-ribose positions. Although other pharmacological reagents result in alterations of the fibroblastic intermediate filaments, cordycepin is unusual because of the rapidity with which the fibroblastic intermediate filaments collapse into the juxtanuclear caps. The juxtanuclear caps have a morphology different from that of the perinuclear bundles of intermediate filaments that arise after long-term depolymerization of the microtubules. The keratin fibers in the epidermal cells retract to a perinuclear ring when treated with cordycepin.
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PMID:Cordycepin rapidly collapses the intermediate filament networks into juxtanuclear caps in fibroblasts and epidermal cells. 245 49