Mechanisms of inhibitions of DNA polymerase gamma by nucleotide analogues having anti-HIV activities.
Inhibition mechanisms of 5'-triphosphates of 3'-azido-3'-deoxythymidine (AZT-TP) and 3'-deoxythymidine (ddTTP) on extensively purified DNA polymerase gamma from bovine testes were examined by analysis of the products synthesized on singly primed M13mp18 single-stranded DNA or synthetic oligonucleotide template-primer in the presence of analogues. The results indicate that AZT-TP inhibits DNA polymerase gamma in competition with dTTP but is not incorporated into DNA, whereas ddTTP is incorporated into DNA and causes chain termination.
Izuta
S
S
Laboratory of Cancer Cell Biology, Nagoya University School of Medicine, Japan.
Saneyoshi
M
M
Sakurai
T
T
Suzuki
M
M
Kojima
K
K
Yoshida
S
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors*; D054306:Dideoxynucleotides; D006678:HIV / Q000187:drug effects; D008297:Male; D013942:Thymine Nucleotides / Q000494:pharmacology*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000998:Antiviral Agents; D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; D015215:Zidovudine; C052873:zidovudine triphosphate; D004258:DNA Polymerase III; C017216:2',3'-dideoxythymidine triphosphate