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Identification of a human cytoplasmic exonuclease: implication in the activity of nucleoside analogs against human immunodeficiency virus type 1 (Meeting abstract).




 

Proc Annu Meet Am Assoc Cancer Res; 35:A2362 1994. Unique Identifier :

Dideoxy nucleoside analogs (ddN) are a class of agents with demonstrated activity against the human immunodeficiency virus (HIV-1). The amount of ddN triphosphate incorporated at the 3'-terminal of the viral genome is a critical determining factor for the anti-HIV action. The extent of incorporation depends on the ability of ddN to serve as substrates for the viral reverse transcriptase (RT) as well as upon their removal from 3'-terminals of DNA in the cytoplasm of an infected cell. A unique 3'-5' exonuclease was isolated from the cytoplasm of human H-9 cells and it was found to remove a variety of structurally diverse nucleoside analog monophosphates from DNA/RNA heteroduplexes. The relative repair differs among the compounds examined (ddCMP greater than D4TMP greater than AZTMP). Similar studies with D and L stereoisomers of novel ddC analogs indicate that L-ddN are less susceptible to this type of repair than D-ddN. The exonucleolytic activity in the cytoplasm may have an impact on the relative anti-HIV potencies as well as on the differential clinical response to ddN analogs.

Cells, Cultured Cytoplasm/*ENZYMOLOGY Exonucleases/*METABOLISM Human HIV-1/*DRUG EFFECTS/ENZYMOLOGY Nucleosides/CHEMISTRY/*PHARMACOLOGY RNA-Directed DNA Polymerase/METABOLISM ABSTRACT



 




Information in this article was accurate in March 30, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.