STIMULATION OF THE PHOSPHORYLATION AND ANTI-HIV ACTIVITY OF PURINE-2',3'-DIDEOXYNUCLEOSIDES BY IMP DEHYDROGENASE INHIBITORS (MEETING ABSTRACT) NLM AIDSLINE Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

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STIMULATION OF THE PHOSPHORYLATION AND ANTI-HIV ACTIVITY OF PURINE-2',3'-DIDEOXYNUCLEOSIDES BY IMP DEHYDROGENASE INHIBITORS (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 32:A2487 1991. Unique Identifier : AIDSLINE ICDB/91675290
Hartman NR; Cooney DA; Ahluwalia GS; Fridland A; Bondoc LL Jr; Mitsuya H; Johns DG; LMC, DCT, NCI, Bethesda, MD 20892

Abstract: Purine-2',3'-dideoxynucleosides (eg, ddGuo, ddAdo) are effective inhibitors of HIV replication. We have found that formation of 5'-mono, di- and triphosphates of these compounds in human T cells is stimulated several-fold by agents which increase intracellular IMP such as ribavirin, tiazofurin and mycophenolic acid. Fold-stimulation of ddNTP formation varied among cell lines, eg, 4-fold in Mold-4 cells with the IMP dehydrogenase inhibitor ribavirin, 10 uM, vs 2-fold in ATH8 cells. With ribavirin, enhancement of anti-HIV activity roughly paralleled the increase in ddNTP formation. The results further support the proposal that the initial step into the phosphorylation of purine-2',3'-dideoxynucleosides (ie, ddN----ddNMP) is catalyzed, at least in part, by a phosphotransferase which utilizes IMP as its phosphate donor.
Keywords: Antineoplastic Agents/*PHARMACOLOGY Dideoxynucleosides/*PHARMACOLOGY HIV/*DRUG EFFECTS IMP Dehydrogenase/*ANTAGONISTS & INHIB Phosphorylation Tumor Cells, Cultured Virus Replication/DRUG EFFECTS ABSTRACT

KWDantineoplasticagents/KWDpharmacologydideoxynucleosides/KWDpharmacologyhiv/KWDdrugeffectsimpdehydrogenase/KWDantagonists&inhibphosphorylationtumorcells,culturedvirusreplication/drugeffectsabstract
911130
M91B0823

Copyright © 1991 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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