Properties of 2′,3′‐dideoxy‐2′,3′‐dehydrothymidine 5′‐triphosphate in terminating DNA synthesis catalyzed by several different DNA polymerases

Abstract

-dehydrothymidine 5'-triphosphate (dddTTP) shows termination substrate properties in the DNA synthesis catalyzed by E. coli DNA polymerase I KF, rat liver DNA polymerase r, reverse transcriptases of avian myeloblastosis virus and Raus sarcoma virus and calf thymus terminal deoxynucleotidyl transferase. This implies that the mononucleotide residue of dddTTP incorporates into 3'-termini of newly synthesized DNA chains. However, dddTTP has no influence on the DNA synthesis catalyzed by calf thymus DNA polymerase ct. In the case of some DNA polymerases dddTTP was one order of magnitude more effective in comparison with the other known termination substrates.

Cellular pharmacology of 2',3'-dideoxy-2',3'-didehydrothymidine, a nucleoside analog active against human immunodeficiency virus

“…One possible explanation is that D4T triphosphate may be a better substrate for reverse transcriptase than is AZT triphosphate, thus causing more efficient termination of chain elongation. Its termination activity has been described, although not with HIV reverse transcriptase and not in comparison to AZT triphosphate (8).…”

Reverse transcriptase and endonuclease activities encoded by Penelope -like retroelements

“…The Penelope RT activity, like that of many other characterized RTs (20)(21)(22), requires divalent cations. The activity is higher in the presence of Mn 2ϩ than Mg 2ϩ , as is the case for murine leukemia virus RT (23), and Mg 2ϩ can be replaced by Zn 2ϩ but not by Ca 2ϩ or Ni 2ϩ (Fig.…”

2′,3′-Didehydro-2′,3′-dideoxythymidine (D4T), an anti-HIV Agent

“…However, Ono et al (1989)showed that substitution of Mg 2 + in the assay with Mn 2 + allows inhibition to be seen with D4T-TP. Dyatkina et al (1987), using oligonucleotide primer extension assays, have shown inhibition can be observed using 500 I-LM D4T-TP and 10I-LM TIP with a-polymerase. Even under these conditions though, D4T does not appear to be irreversibly incorporated since addition of more TIP results in further extension of the DNA fragments.…”

“…Matthes et al (1987) find D4T-TP to be 3D-fold more potent than AZT-TP against the (3-polymerase, and Ono et al (1989) also find D4T-TP to be more inhibitory to this enzyme. It has been claimed (Dyatkina et al, 1987) that with (3-polymerase, D4T-TP is incorporated into DNA and terminates chain extension. There was no dose-effect, however, since no difference in termination fragments was seen at a range of D4T-TP concentrations covering two orders of magnitude.…”