Browse by author
Lookup NU author(s): Professor Olaf Heidenreich
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
In the presence of oligo(dT).poly(rA) as primer-template, 3'-azidothymidine triphosphate (N3'(3)-ddTTP) is a substrate for human immunodeficiency virus 1 reverse transcriptase with an apparent Km value of 3.0 microM. This compares with an apparent Km for thymidine monophosphate (dTMP) incorporation of 2.5 microM. The apparent Vmax value for 3'-azidothymidine monophosphate (N3'(3)-ddTMP) incorporation is 50 times lower than that of dTMP incorporation. Kinetic analysis of the inhibition of reverse transcriptase by N3'(3)-ddTTP shows competitive inhibition with thymidine triphosphate (dTTP) with a Ki of 41 nM and an uncompetitive pattern of inhibition with template-primer having a Ki of 140 nM. This indicates incorporation of the analogue into the primer and inhibition of the enzyme by formation of a dead-end complex. The 3'-azidothymidine-terminated primer-template [N3'(3)-ddT-(dT)15.poly(rA)] is a potent competitive inhibitor versus primer-template with a Ki of 2.4 nM and shows mixed-type inhibition against dTTP with a Ki of 8 nM. The low inhibition constant for this chain-terminated primer suggests that such oligonucleotides can act as potent inhibitors of enzyme catalysis.
Author(s): Heidenreich O, Kruhoffer M, Grosse F, Eckstein F
Publication type: Article
Publication status: Published
Journal: European Journal of Biochemistry
Print publication date: 24/09/1990
ISSN (print): 1742-464X
ISSN (electronic): 1742-4658
PubMed id: 1698626
Notes: Comparative Study
Research Support, Non-U.S. Gov't