Introduction of the alpha-P-borano-group into deoxynucleoside triphosphates increases their selectivity to HIV-1 reverse transcriptase relative to DNA polymerases.
A series of 2'-deoxynucleoside 5'-triphosphates (dNTPs) and their alpha-P-thio or alpha-P-borano analogues, i.e., (Sp-dNTPalphaS), (Rp-dNTPalphaB) and (Sp-dNTPalphaB) were studied as substrates for DNA dependent DNA polymerases and HIV-1 reverse transcriptase (RT). For HIV-1 RT the Rp-dNTPalphaB 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 alpha-boranophosphate group into dNTPs increases their selectivity to HIV-1 RT relative to bacterial DNA polymerases.
Dobrikov
Mikhail I
MI
Department of Chemistry, P.M. Gross Chemical Laboratory, Duke University, Durham, North Carolina 27708, USA.
Grady
Kristen M
KM
Shaw
Barbara Ramsay
BR
D001896:Boron Compounds / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004256:DNA Polymerase I / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D003845:Deoxycytosine Nucleotides / Q000138:chemical synthesis / Q000378:metabolism*; D054303:HIV Reverse Transcriptase / Q000378:metabolism*; D007700:Kinetics; D013237:Stereoisomerism; D019914:Taq Polymerase / Q000378:metabolism
D001896:Boron Compounds; D003845:Deoxycytosine Nucleotides; C024107:2'-deoxycytidine 5'-triphosphate; D004247:DNA; D019914:Taq Polymerase; D054303:HIV Reverse Transcriptase; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase