ddC- and 3TC-bis(SATE) monophosphate prodrugs overcome cellular resistance mechanisms to HIV-1 associated with cytidine kinase deficiency.
A 2',3'-dideoxycytidine (ddC)-resistant T-lymphoid cell line (MOLT-4/8rddC250), in which deoxycytidine kinase (dCK) gene-expression was decreased when compared with parental cells, has been selected. Cytotoxic and antiretroviral activity of ddC and 3TC was significantly lower in MOLT-4/8rddC250-than in parental MOLT-4/8 cells. ddC- and 3TC-bis(SATE)phosphotriesters completely overcame cellular resistance mechanisms and showed comparable both cytotoxic and antiretroviral activity in parental and ddC-resistant cells.
Gröschel
B
B
Institute of Medical Virology, Johann Wolfgang Goethe University Frankfurt/M., Germany.
Himmel
N
N
Cinatl
J
J
Périgaud
C
C
Gosselin
G
G
Imbach
J L
JL
Doerr
H W
HW
Cinatl
J
J
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D003842:Deoxycytidine Kinase / Q000172:deficiency* / Q000235:genetics; D004352:Drug Resistance, Microbial; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016047:Zalcitabine / Q000494:pharmacology*
D017931:DNA Primers; D011355:Prodrugs; D019259:Lamivudine; D016047:Zalcitabine; D003842:Deoxycytidine Kinase