Inhibitory effect of N3-methyl derivative of 3'-azido-3'-deoxythymidine 5'-triphosphate on the activity of HIV-1 reverse transcriptase.
N3-Methyl derivative of 3'-azido-3'-deoxythymidine 5'-triphosphate (Me-AZTTP) showed a potent inhibitory effect on HIV-1 reverse transcriptase using MS2 phage RNA as the template. The inhibition mechanism of MeAZTTP was noncompetitive with respect to any of the template MS2 RNA, dATP and dCTP. On the other hand, MeAZTTP showed a mixed-type inhibition with respect to dGTP and dTTP. These results indicate that MeAZTTP competes not only with dTTP but also with dGTP.
Nakane
H
H
Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Suzuki
A
A
Nakata
Y
Y
Kitade
Y
Y
Hirota
K
K
Maki
Y
Y
Ono
K
K
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001435:Bacteriophages / Q000235:genetics; D054306:Dideoxynucleotides; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D008745:Methylation; D012367:RNA, Viral / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors; D013698:Templates, Genetic; D013942:Thymine Nucleotides / Q000494:pharmacology*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000998:Antiviral Agents; D054306:Dideoxynucleotides; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; C077692:N(3)-methyl-3'-azido-3'-deoxythymidine 5'-triphosphate; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase