title: ddC- and 3TC-bis(SATE) monophosphate prodrugs overcome cellular resistance mechanisms to HIV-1 associated with cytidine kinase deficiency.
abstract: 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.
authors.affiliation: Institute of Medical Virology, Johann Wolfgang Goethe University Frankfurt/M., Germany.
authors.forename: B
authors.initials: B
authors.lastname: Gröschel
authors.forename: N
authors.initials: N
authors.lastname: Himmel
authors.forename: J
authors.initials: J
authors.lastname: Cinatl
authors.forename: C
authors.initials: C
authors.lastname: Périgaud
authors.forename: G
authors.initials: G
authors.lastname: Gosselin
authors.forename: J L
authors.initials: JL
authors.lastname: Imbach
authors.forename: H W
authors.initials: HW
authors.lastname: Doerr
authors.forename: J
authors.initials: J
authors.lastname: Cinatl
mesh_terms: 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*
chemical_list: D017931:DNA Primers; D011355:Prodrugs; D019259:Lamivudine; D016047:Zalcitabine; D003842:Deoxycytidine Kinase