Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone
dc.contributor.author | Turk, Steven R. | en_US |
dc.contributor.author | Shipman, Charles Jr. | en_US |
dc.contributor.author | Drach, John C. | en_US |
dc.date.accessioned | 2006-04-07T19:31:40Z | |
dc.date.available | 2006-04-07T19:31:40Z | |
dc.date.issued | 1986-05-01 | en_US |
dc.identifier.citation | Turk, Steven R., Shipman, Jr., Charles, Drach, John C. (1986/05/01)."Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone." Biochemical Pharmacology 35(9): 1539-1545. <http://hdl.handle.net/2027.42/26189> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T4P-4751TG6-1KT/2/d50b0398ab1bab5bd6aff9b8f61dd1b3 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/26189 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=3011019&dopt=citation | en_US |
dc.description.abstract | The effects of thiosemicarbazone derivatives of 2-acetylpyridine on mammalian and viral ribonucleoside diphosphate reductases were investigated. The enzymes were partially purified from uninfected and herpes simplex virus type-1 (HSV-1)-infected KB cells by sequential salt fractionation with streptomycin sulfate and ammonium sulfate and by affinity chromatography on ATP-agarose. The five thiosemicarbazone derivatives investigated were all potent inhibitors of the virus-induced reductase. Fifty percent inhibitory concentrations (50 values) range from 2 to 13 [mu]M. Four of the five derivatives also were inhibitors of the host cell reductase . A semicarbazone was inactive against the cellular enzyme and relatively weak as an inhibitor of the viral enzyme . Four of the six compounds were preferential inhibitors of the viral reductase based on a comparison of 50 values (5- to > 85-fold difference). Kinetic experiments revealed that inhibition of the HSV-1 reductase by the thiosemicarbazones was noncompetitive with respect to CDP and dithiothreitol. A comparison of the inhibitory effects of 2-acetylpyridine thiosemicarbazone itself on viral reductase and on virus replication in vitro demonstrated a similarity in the dose-response relationships for the two parameters. This observation supports the hypothesis that the HSV-induced ribonucleoside diphosphate reductase is an important target for the design of antiviral drugs. | en_US |
dc.format.extent | 871581 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Interdepartmental Graduate Program in Medicinal Chemistry and Department of Oral Biology, School of Dentistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Interdepartmental Graduate Program in Medicinal Chemistry and Department of Oral Biology, School of Dentistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Interdepartmental Graduate Program in Medicinal Chemistry and Department of Oral Biology, School of Dentistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.identifier.pmid | 3011019 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/26189/1/0000268.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0006-2952(86)90122-X | en_US |
dc.identifier.source | Biochemical Pharmacology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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