Reverse transcriptional mutagenesis induced by ribonucleoside triphosphate analogue, PTP and its availability for anti-HIV-1 therapy.
The bicyclic pyrimidine analogue, 3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one (P) can base pair with both A and G. The riboside 5'-triphsophate of P (PTP) efficiently induces mutation during in vitro transcription and reverse transcription cycles using a phage promoter. In the present study, we have constructed an in vitro transcription system promoted by the human immunodeficiency virus type 1 (HIV-1) 5'-long terminal repeat (LTR) using HeLa nuclear extract supplemented with HIV-1 Tat protein. Using this system, the effects of mutagenic ribonucleotide analogues were studied.
Moriyama
K
K
Gene Research Center, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Okada
T
T
Loakes
D
D
Miyano-Kurosaki
N
N
Takaku
H
H
Negishi
K
K
D019380:Anti-HIV Agents / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D016296:Mutagenesis; D009153:Mutagens / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D012265:Ribonucleotides / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D014158:Transcription, Genetic
C476366:6-(2-ribofuranosyl)-3,4-dihydro-8H-pyrimido(4,5-c)(1,2)oxazin-7-one 5'-triphosphate; D019380:Anti-HIV Agents; D009153:Mutagens; D012265:Ribonucleotides; D012194:RNA-Directed DNA Polymerase