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.