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

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

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 : AIDSLINE ICDB/95604047
Skalski V; Liu SH; Cheng YC; Dept. of Pharmacology, Yale University School of Medicine, New; Haven CT 06510

Abstract: 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.

Keywords: Cells, Cultured Cytoplasm/*ENZYMOLOGY Exonucleases/*METABOLISM Human HIV-1/*DRUG EFFECTS/ENZYMOLOGY Nucleosides/CHEMISTRY/*PHARMACOLOGY RNA-Directed DNA Polymerase/METABOLISM ABSTRACT
950330
M9530824

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