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

Abstract

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 × 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.

ACKNOWLEDGMENTS

We thank the Japan Society for the Promotion of Science Grants-in-aid for JSPS fellows (no. 7807) (to KM) and Nycomed Amersham plc (to DL) for financial assistance, Dr. Dan Brown for his advice and helpful discussions and Prof. Hikoya Hayatsu for kind support.