Metabolism of arabinosyladenine in herpes simplex virus-infected and uninfected cells : Correlation with inhibition of DNA synthesis and role in antiviral selectivity
dc.contributor.author | Schwartz, Pauline M. | en_US |
dc.contributor.author | Novack, Jean M. | en_US |
dc.contributor.author | Shipman, Charles Jr. | en_US |
dc.contributor.author | Drach, John C. | en_US |
dc.date.accessioned | 2006-04-07T18:25:37Z | |
dc.date.available | 2006-04-07T18:25:37Z | |
dc.date.issued | 1984-08-01 | en_US |
dc.identifier.citation | Schwartz, Pauline M., Novack, Jean, Shipman, Jr., Charles, Drach, John C. (1984/08/01)."Metabolism of arabinosyladenine in herpes simplex virus-infected and uninfected cells : Correlation with inhibition of DNA synthesis and role in antiviral selectivity." Biochemical Pharmacology 33(15): 2431-2438. <http://hdl.handle.net/2027.42/24750> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T4P-4748W9M-D/2/148433c321461f7cde1b000293ab24c1 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/24750 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=6087827&dopt=citation | en_US |
dc.description.abstract | The metabolism of 9-[beta]--arabinofuranosyladenine (ara-A, vidarabine) and its effects on DNA synthesis were compared in uninfected and herpes simplex virus type-1 (HSV-1)-infected KB cells. In the absence of an inhibitor of adenosine deaminase, ara-A was deaminated to 9-[beta]--arabinofuranosylhypoxanthine and phosphorylated to ara-A-5'-mono-, di- and triphosphates in both types of cells. When an inhibitor of adenosine deaminase (coformycin) was added to cell cultures, nucleotides were the only metabolites detected--primarily the 5'-triphosphate of ara-A (aATP). Detailed studies performed in the presence of coformycin established that the net rate and extent of aATP formation were the same in uninfected and HSV-1-infected cells. After a 12-hr exposure to 50 [mu]M ara-A, intracellular concentrations of aATP were approximately 40 [mu]M. Levels of aATP correlated directly with inhibition of total DNA synthesis. Approximately 0.7 [mu]M aATP was required for 50% inhibition of total DNA synthesis in both uninfected and HSV-1-infected cells. Following removal of ara-A-containing culture medium, aATP levels in uninfected cells declined with a half-life of 3.2 hr. In marked contrast, the half-life in HSV-1-infected cells was 9.3 hr; this may explain why as little as a 3-hr exposure to ara-A resulted in a significant HSV-1 titer reduction. Taken together, the data show that when ara-A was removed from culture medium, levels of aATP persisted longer in HSV-1-infected cells thereby prolonging antiviral activity. This effect could be important in vivo where levels of ara-A oscillate with dosing schedule. | en_US |
dc.format.extent | 774897 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 | Metabolism of arabinosyladenine in herpes simplex virus-infected and uninfected cells : Correlation with inhibition of DNA synthesis and role in antiviral selectivity | 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 | School of Dentistry and Interdepartmental Graduate Program in Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | School of Dentistry and Interdepartmental Graduate Program in Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | School of Dentistry and Interdepartmental Graduate Program in Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | School of Dentistry and Interdepartmental Graduate Program in Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.identifier.pmid | 6087827 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/24750/1/0000172.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0006-2952(84)90715-9 | en_US |
dc.identifier.source | Biochemical Pharmacology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.