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Synthesis, and in vitro Enzymatic and Antiviral Evaluation of d4T Polyphosphate Derivatives as Chain Terminators
Author(s) -
Yang Shiqiong,
Pannecouque Christophe,
Herdewijn Piet
Publication year - 2012
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201200250
Subject(s) - polyphosphate , in vitro , chemistry , enzyme , hydrolysis , biochemistry , human immunodeficiency virus (hiv) , phosphate , virology , biology
A series of d4T di‐ or triphosphate derivatives have been synthesized and evaluated as effective substrates for HIV‐1 RT, and also tested for their in vitro anti‐HIV activity. The steady‐state kinetic study of compounds 1 – 4 in an enzymatic incorporation assay by HIV‐1 RT follows MichaelisMenten profile. In addition, compounds 2 – 4 are able to inhibit HIV‐1 replication to the same extent as d4T and d4TMP in MT‐4 cells, as well as in CEM/0 cells and CEM/TK − cells. The data suggests that these d4T polyphosphate derivatives are hydrolyzed to d4T and rephosphorylated to d4TTP before exerting their antiviral activity.