Synthesis of acyclothymidine triphosphate and alpha-P-boranotriphosphate and their substrate properties with retroviral reverse transcriptase.
[reaction: see text] The first example of an acyclonucleoside alpha-P-boranotriphosphate has been synthesized via a phosphoramidite approach in a one-pot reaction with good yield. The presence of the alpha-P-BH(3) in 5b results in a 9-fold increase in efficiency of incorporation by MMLV retroviral reverse transcriptase relative to non-boronated 5a in pre-steady-state conditions. The preliminary results indicate that acyclonucleoside alpha-P-boranotriphosphates may have promising applications as a probe of enzyme mechanisms and in the design of new antiviral drugs.
Li
Ping
P
Department of Chemistry, Box 90346, Duke University, Durham, North Carolina 27708-0346, USA.
Dobrikov
Mikhail
M
Liu
Hongyan
H
Shaw
Barbara Ramsay
BR
D001896:Boron Compounds / Q000138:chemical synthesis* / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000201:enzymology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D013379:Substrate Specificity; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism
D001896:Boron Compounds; D014498:Uracil; C046151:N-(2-(hydroxyethoxy)methyl)-5-methyluracil; D012194:RNA-Directed DNA Polymerase