Highly efficient random mutagenesis in transcription-reverse-transcription cycles by a hydrogen bond ambivalent nucleoside 5'-triphosphate analogue: potential candidates for a selective anti-retroviral therapy.
The nucleoside P can base pair with both A and G. We evaluated the mutation frequency induced by the 5'-triphospbate of the ribonucleoside P (PTP) in an in vitro retroviral replication model. After 4 cycles of replication in the presence of PTP, the mutation frequency was raised to 3.8 x 10(-2) per nucleotide and C-to-U and U-to-C mutations were dominantly observed. These results suggest that ambivalent NTP analogues, like PTP, could induce mutations beyond the error threshold of retroviruses.
Moriyama
K
K
Gene Research Center, Okayama University, Tsushima, Japan.
Otsuka
C
C
Loakes
D
D
Negishi
K
K
D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D006860:Hydrogen Bonding; D008954:Models, Biological; D016296:Mutagenesis / Q000187:drug effects* / Q000235:genetics; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology*; D010957:Plasmids / Q000096:biosynthesis / Q000235:genetics; D012190:Retroviridae / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D014158:Transcription, Genetic / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
D000998:Antiviral Agents; D009705:Nucleosides; C034510:CTCGAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific