SELECTIVE ACTION OF 2',3'-DIDEHYDRO-2',3'-DIDEOXYTHYMIDINE TRIPHOSPHATE ON HIV REVERSE TRANSCRIPTASE AND HUMAN DNA POLYMERASES (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

SELECTIVE ACTION OF 2',3'-DIDEHYDRO-2',3'-DIDEOXYTHYMIDINE TRIPHOSPHATE ON HIV REVERSE TRANSCRIPTASE AND HUMAN DNA POLYMERASES (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 32:A2369 1991. Unique Identifier : AIDSLINE ICDB/91675172
Huang P; Farquhar D; Plunkett W; Univ. of Texas M.D. Anderson Cancer Center, Houston, TX 77030

Abstract: 2',3'-Didehydro-2',3'-dideoxythymidine (D4T) is a nucleoside analog with potent and selective anti-HIV activity. The action of D4T triphosphate (D4T-TP) on DNA strand elongation catalyzed by HIV reverse transcriptase and human DNA polymerases was evaluated in comparison with the action of 3'-azido-3'-deoxythymidine triphosphate (AZT-TP). Sequencing gel analysis demonstrated that the HIV reverse transcriptase preferentially incorporated D4T-TP into the T sites of the growing DNA strands and terminated DNA synthesis at these sites. Almost all of the DNA strands were terminated within the first 15 T sites in the presence of equal molar concentrations of D4T-TP and dTTP. This chain termination effect is as potent as that of AZT-TP. In contrast, human DNA polymerases alpha and epsilon incorporated substantially less, but detectable, amounts of D4T-TP into DNA with Km values of 11 uM and 17 uM, respectively. However, 1 uM dTTP was able to effectively compete with 30 uM D4T-TP and supported the synthesis of high mol wt DNA by polymerases alpha and epsilon.

Keywords: Antiviral Agents/*PHARMACOLOGY Comparative Study Dideoxynucleosides/*PHARMACOLOGY DNA Polymerase II/*METABOLISM DNA Polymerases/*METABOLISM DNA Replication/DRUG EFFECTS Human HIV/DRUG EFFECTS/*ENZYMOLOGY Kinetics RNA-Directed DNA Polymerase/*METABOLISM Thymine Nucleotides/*PHARMACOLOGY Zidovudine/*ANALOGS & DERIVATIVES/PHARMACOLOGY ABSTRACT
910930
M9190726

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