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)

The quinone intermediates resulting from tyrosinase-mediated oxidation of tyrosine were evaluated as sulfhydryl reagent inhibitors of purified calf thymus DNA polymerase alpha in order to determine which of these might be cytotoxic. Dopachrome and an oxidation product of 2,4,5-trihydroxyphenylalanine were relatively ineffective as inhibitors of DNA polymerase alpha. On the other hand, a dopaquinone analogue, 4-(2-N-acetylaminoethyl)-1,2-benzoquinone, synthesized from N-acetyl dopamine, was demonstrated to have marked affinity for this sulfhydryl enzyme. This property was shared by 1,2-benzoquinone. These studies point to dopaquinone as a significant toxic metabolite in melanin biosynthesis.
J Invest Dermatol 1978 Feb
PMID:The toxicity of melanin precursors. 41 70

L-dopa methyl ester has been shown to be an effective antitumor agent against the B-16 melanoma in vivo. We have now examined the analog, dopamine, a major catabolite of L-dopa. Dopamine administration at a daily dose of 600 mg/kg resulted in a 48% (p less than .001) increase in survival of treated mice as compared to non-treated controls. In vitro, an effect similar to that observed with L-dopa methyl ester was noted, specifically, a rapid and profound inhibition of thymidine incorporation with little effect on uridine or leucine incorporation. We have postulated that the inhibition of a DNA polymerase might be the site of action of these novel antitumor agents.
J Invest Dermatol 1978 Aug
PMID:Dopamine: a novel antitumor agent active against B-16 melanoma in vivo. 68 87

Herpes simplex virus DNA was identified by the polymerase chain reaction with primers specific for the herpes DNA polymerase gene. A herpes-specific amplimer was detected in two of three cases in which the clinical and histologic features were inconclusive.
J Am Acad Dermatol 1991 May
PMID:Herpes simplex virus DNA in occult lesions: demonstration by the polymerase chain reaction. 165 53

We report a case of orofacial herpes simplex virus (HSV) infection that was progressive despite multiple courses of acyclovir sodium in a patient with the acquired immunodeficiency syndrome. The viral isolate was shown to be resistant to acyclovir in vitro, but proved susceptible to vidarabine and foscarnet sodium (trisodium phosphonoformate). The patient failed to respond to a 2-week course of intravenous vidarabine. However, rapid improvement in the orofacial lesion occurred with intravenous foscarnet. Most HSV isolates that are resistant to acyclovir are spontaneous mutants partially or completely lacking in thymidine kinase. Because foscarnet is a direct inhibitor of HSV DNA polymerase, this compound is expected to have efficacy against acyclovir-resistant strains. This report documents successful treatment of clinically significant HSV with intravenous administration of foscarnet, suggesting that further study is indicated.
Arch Dermatol 1989 Nov
PMID:Successful treatment of progressive acyclovir-resistant herpes simplex virus using intravenous foscarnet in a patient with the acquired immunodeficiency syndrome. 255 19

A screening program for antiviral drugs begun at Burroughs Wellcome in the 1960s resulted in the discovery of acyclovir in 1974. Preclinical investigation brought the drug to clinical trials in 1977 and the first form of the drug (topical) was available to physicians in 1982. Activity of acyclovir is greatest against herpes 1 and herpes 2, less against varicella zoster, still less against Epstein-Barr, and very little against cytomegalovirus. Acyclovir is an antiviral agent only after it is phosphorylated in infected cells by a viral-induced thymidine kinase. Acyclovir monophosphate is phosphorylated to diphosphate and triphosphate forms by cellular enzymes in the infected host cell where the drug is concentrated. Acyclovir triphosphate inactivates viral deoxyribonucleic acid polymerase. Acyclovir incorporation into the growing viral deoxyribonucleic acid chain causes its termination. The antiviral process has relatively little effect on normal, uninfected cells. An important toxic effect of acyclovir is its potential to cause obstructive nephropathy. The drug is excreted primarily by the kidney, which may require smaller doses in patients with decreased kidney function. Oral dosages of acyclovir as recommended for herpes simplex are probably not adequate for varicella zoster infections.
J Am Acad Dermatol 1988 Jan
PMID:History, pharmacokinetics, and pharmacology of acyclovir. 282 40

The genome of herpes simplex virus codes for several enzymes, including viral thymidine kinase and viral deoxyribonucleic acid (DNA) polymerase. When viral resistance develops, it does so by changes in these two enzymes. Three possible mechanisms of viral resistance to acyclovir include (1) selection of viral mutants that make little or no thymidine kinase and do not phosphorylate acyclovir adequately, (2) selection of mutants that can phosphorylate thymidine but cannot phosphorylate acyclovir (i.e., these viruses have thymidine kinases with altered substrate specificity), and (3) selection of viruses that have altered DNA polymerases that replicate viral DNA in the presence of acyclovir triphosphate. Thymidine kinase-deficient virus has been isolated from clinical isolates frequently, but few strains appear to be virulent for animals or humans and only a few seem to have caused clinical disease. Viruses with altered substrate specificity have been reported but viruses with an altered DNA polymerase have not occurred in clinical practice. Antiviral drugs should be used only when necessary to minimize the appearance of resistant strains of virus.
J Am Acad Dermatol 1988 Jan
PMID:Significance of resistance of herpes simplex virus to acyclovir. 282 41

Bacteriophage M13 mp10 DNA were irradiated with near-UV light in the presence of tetracycline derivatives and primed with synthetic oligonucleotide to be used for DNA synthesis using Escherichia coli DNA polymerase. Chain terminations were observed by denaturing polyacrylamide gel electrophoresis and mapped precisely. All the synthesis stops occurred before or at the level of guanine residues, showing that the photoreaction mediated by tetracycline derivatives led to a preferential alteration of guanine residues. These lesions were demonstrated to be induced in DNA through a pathway involving singlet oxygen. Tetracycline derivatives also photoinduced the breakage of the DNA sugar-phosphate backbone monitored by the conversion of supercoiled phi X174 DNA to a relaxed form. This lesion was shown to be initiated by hydroxyl radicals. The production of this free radical has been confirmed by electron paramagnetic resonance (EPR) spin trapping experiments using 5,5-dimethyl-1-pyrroline-N-oxide as spin trap. In addition to the EPR signal due to OH radicals trapping another unassigned signal has been detected.
J Invest Dermatol 1986 Jun
PMID:DNA alterations photosensitized by tetracycline and some of its derivatives. 301 16

DNA polymerase activity was determined in hyperkeratotic epidermis of the guinea pig by topical application of n.hexadecane. Epidermal cells were separated by Percoll gradient centrifugation. DNA polymerase alpha activity was higher in the basal cells, but polymerase beta activity was higher in granular cells than in cells from the other layers. The hyperkeratosis was accompanied by an increase in polymerase alpha activity in both the squamous and basal cells. However, polymerase beta activity decreased in the granular cells and was distributed almost uniformly across the epidermis. The distribution pattern of polymerase activities in the hyperkeratotic epidermis was not simply an enhancement of the pattern in normal epidermis.
Arch Dermatol Res 1986
PMID:DNA polymerase activity in the n.hexadecane-induced hyperkeratotic epidermis. 301 56

Reusable needle electrodes have been standard for electrodesiccation procedures commonly done by dermatologists. This study investigates the risk of transmission of hepatitis B virus by such electrodes during simulated use with electrodesiccation. Sterile needle electrodes were inoculated with either purified hepatitis B surface antigen (HBsAg+) concentrate or serum positive for both HBsAg and deoxyribonucleic acid (DNA) polymerase activity (a measure of infectious and replicating hepatitis B virus), followed by simulated use for electrodesiccation at various settings and rinsing of the tip with negative serum. The rinse serum was then assayed for HBsAg, DNA polymerase activity, and the presence of viral particles by electron microscopy. HBsAg could be transferred through the electrodesiccation procedure at all settings used. Although DNA polymerase activity was negative in the rinse serum, electron microscopy demonstrated transfer of HBsAg forms and complete virus. These results suggest a potential risk of spread of hepatitis B virus by reusable needle electrodes for electrodesiccation.
J Am Acad Dermatol 1986 Dec
PMID:Transfer of hepatitis B virus by contaminated reusable needle electrodes after electrodesiccation in simulated use. 380 65

The effect of several antiviral drugs on the reactivation of herpes simplex virus type 1 in explant cultures of latently infected mouse trigeminal ganglia was investigated. Phosphonoacetate and phosphonoformate, which act directly on the virus-induced DNA polymerase, require a drug concentration of 400 micrograms/ml for the inhibition of virus reactivation in latently infected ganglia. Arabinosyladenine and arabinosyladenine monophosphate, which are phosphorylated to triphosphates by cellular enzymes and inhibit virus synthesis either by blocking the DNA polymerase or by incorporation into viral DNA, require a concentration of only 100 micrograms/ml for the inhibition of the reactivation process. Drugs that are phosphorylated by the virus-induced thymidine kinase, such as acyclovir, arabinosylthymine, bromovinyldeoxyuridine, and three fluorinated pyrimidine nucleosides require the lowest drug concentrations for complete inhibition of virus reactivation in latently infected ganglia explant cultures. Our data suggest that the inhibition of virus reactivation is dependent not only on drug concentration, but also on the number of latently infected neurons in the ganglia.
J Invest Dermatol 1984 Nov
PMID:Effect of eight antiviral drugs on the reactivation of herpes simplex virus in explant cultures of latently infected mouse trigeminal ganglia. 620 91


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