Deoxythreosyl Phosphonate Nucleosides as Selective Anti-HIV Agents
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- 作者：Tongfei Wu ; Matheus Froeyen ; Veerle Kempeneers ; Christophe Pannecouque ; Jing Wang ; Roger Busson ; Erik De Clercq ; and Piet Herdewijn
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：April 13, 2005
- 年：2005
- 卷：127
- 期：14
- 页码：5056 - 5065
- 全文大小：281K
- 年卷期：v.127,no.14(April 13, 2005)
- ISSN：1520-5126
文摘
Out of a series of eight new phosphonate nucleosides with an L-threose and an L-2-deoxythreosesugar moiety, two new compounds were identified (PMDTA and PMDTT) that showed potent anti-HIV-1(HIV-2) activity [EC50 = 2.53 
M (PMDTA) and 6.59 M (PMDTT)], while no cytoxicity was observed at thehighest concentration tested [CC50 > 316 M (PMDTA) and > 343 M (PMDTT)]. The kinetics ofincorporation of PMDTA into DNA (using the diphosphate of PMDTA as substrate and HIV-1 reversetranscriptase as catalyst) was similar to the kinetics observed for dATP, while the diphosphate of PMDTAwas a very poor substrate for DNA polymerase 
. The incorporated PMDTA fits very well in the active sitepocket of HIV-1 reverse transcriptase.
M (PMDTA) and 6.59 M (PMDTT)], while no cytoxicity was observed at thehighest concentration tested [CC50 > 316 M (PMDTA) and > 343 M (PMDTT)]. The kinetics ofincorporation of PMDTA into DNA (using the diphosphate of PMDTA as substrate and HIV-1 reversetranscriptase as catalyst) was similar to the kinetics observed for dATP, while the diphosphate of PMDTAwas a very poor substrate for DNA polymerase . The incorporated PMDTA fits very well in the active sitepocket of HIV-1 reverse transcriptase.