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Title: Deoxythreosyl phosphonate nucleosides as selective anti-HIV agents
Authors: Wu, Tongfei ×
Froeyen, Mathy
Kempeneers, V
Pannecouque, Christophe
Wang, J
Busson, Roger
De Clercq, Erik
Herdewijn, Piet #
Issue Date: 2005
Series Title: Journal of the American Chemical Society vol:127 issue:14 pages:5056-5065
Abstract: Out of a series of eight new phosphonate nucleosides with an l-threose and an l-2-deoxythreose sugar moiety, two new compounds were identified (PMDTA and PMDTT) that showed potent anti-HIV-1 (HIV-2) activity [EC50 = 2.53 microM (PMDTA) and 6.59 microM (PMDTT)], while no cytoxicity was observed at the highest concentration tested [CC50 > 316 microM (PMDTA) and > 343 microM (PMDTT)]. The kinetics of incorporation of PMDTA into DNA (using the diphosphate of PMDTA as substrate and HIV-1 reverse transcriptase as catalyst) was similar to the kinetics observed for dATP, while the diphosphate of PMDTA was a very poor substrate for DNA polymerase alpha. The incorporated PMDTA fits very well in the active site pocket of HIV-1 reverse transcriptase.
URI: 
ISSN: 0002-7863
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
Biocrystallography
Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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