Abstract
A series of 2′-deoxynucleoside 5′-triphosphates (dNTPs) and their α-P-thio or α-P-borano analogues, i.e., (Sp-dNTPαS), (Rp-dNTPαB) and (Sp-dNTPαB) were studied as substrates for DNA dependent DNA polymerases and HIV-1 reverse transcriptase (RT). For HIV-1 RT the Rp-dNTPαB isomers are 1.2-fold better substrates than natural dNTPs. For DNA polymerases their efficiencies of incorporation are 3-fold (Klenow, Sequenase) and 5-fold (Taq) lower than for dNTPs. Thus, introduction of the α-boranophosphate group into dNTPs increases their selectivity to HIV-1 RT relative to bacterial DNA polymerases.
Acknowledgments
The authors thank Dr. D. Sergueev for synthesis of the fluorescent-labeled oligonucleotides. This investigation was supported by NIH grants R01 GM 37693 and A1-52061 to B.R.S.