       Document 0246
 DOCN  M9640246
 TI    Effects of non-nucleoside inhibitors of human immunodeficiency virus
       type 1 in cell-free recombinant reverse transcriptase assays.
 DT    9604
 AU    Gu Z; Quan Y; Li Z; Arts EJ; Wainberg MA; McGill University AIDS Centre,
       Lady Davis Institute-Jewish; General Hospital, Montreal, Quebec, Canada.
 SO    J Biol Chem. 1995 Dec 29;270(52):31046-51. Unique Identifier : AIDSLINE
       MED/96125081
 AB    We have employed a cell-free human immunodeficiency virus type 1 (HIV-1)
       reverse transcriptase (RT) assay to study the effects of non-nucleoside
       inhibitors of RT (NNRTI) by directly monitoring specific HIV DNA
       products using a HIV-1 genome-derived template and an
       oligodeoxynucleotide primer. As previously shown by ourselves and
       others, nucleoside analog triphosphates, e.g. 3'-azido-3'-deoxythymidine
       triphosphate and 2',3'-dideoxyadenosine triphosphate, could directly
       inhibit HIV RT RNA-dependent DNA polymerase activity by causing chain
       termination, as visualized in a RT reaction that yields specific DNA
       products. In contrast, each of two NNRTIs, nevirapine and delavirdine,
       directly inhibited RT activity without causing chain termination
       effects. We also analyzed interactions between nucleoside analogs and
       NNRTIs or among NNRTIs by chain elongation/dNTP incorporation and/or
       steady-state kinetic assays. Combinations of nevirapine with the
       triphosphates of either the (-)-strand of 2',3'-dideoxy-3'-thiacytidine
       or 2',3'-dideoxyadenosine yielded additive/synergistic effects on RT
       activity. However, only an additive effect was observed when
       combinations of nevirapine and 3'-azido-3'-deoxythymidine triphosphate
       were employed. Combinations of nevirapine and delavirdine had an
       antagonistic effect on the inhibition of HIV-1 RT activity.
 DE    Cell-Free System  Deoxycytosine Nucleotides/PHARMACOLOGY  Drug
       Antagonism  Drug Synergism  HIV-1/*DRUG EFFECTS  Indoles/PHARMACOLOGY
       Piperazines/PHARMACOLOGY  Pyridines/PHARMACOLOGY  Reverse Transcriptase
       Inhibitors/*PHARMACOLOGY  RNA-Directed DNA Polymerase/*DRUG EFFECTS
       Support, Non-U.S. Gov't  Thymine Nucleotides/PHARMACOLOGY
       Zidovudine/ANALOGS & DERIVATIVES/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

