Document 0088
 DOCN  M9440088
 TI    Viral resistance to the thiazolo-iso-indolinones, a new class of
       nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse
       transcriptase.
 DT    9404
 AU    Maass G; Immendoerfer U; Koenig B; Leser U; Mueller B; Goody R; Pfaff E;
       Bundesforschungsanstalt fur Viruskrankheiten der Tiere,; Tubingen,
       Germany.
 SO    Antimicrob Agents Chemother. 1993 Dec;37(12):2612-7. Unique Identifier :
       AIDSLINE MED/94153035
 AB    Thiazolo-iso-indolinone derivatives with high specificity toward the
       reverse transcriptase (RT) of human immunodeficiency virus type 1
       (HIV-1) were identified. The most potent compound, BM +51.0836,
       inhibited HIV-1 RT at a 50% inhibitory concentration of 90 nM in vitro.
       In cell culture assays, similar 50% inhibitory concentrations were
       obtained with high specificity for HIV-1. These substances were equally
       active against a zidovudine-resistant isolate. No antiviral effect was
       observed with an HIV-2 isolate. HIV-1 isolates resistant to the
       thiazolo-iso-indolinones were generated in cell culture, and the
       nucleotide sequences of the respective RT genes were analyzed
       subsequently. Comparison of the deduced amino acid sequences with the
       wild-type sequence showed an amino acid change at position 181 (Tyr to
       Cys). Substitutions of amino acid Lys-101 and Lys-103 as well as Tyr-181
       and/or Tyr-188 by site-directed mutagenesis led to resistance against
       the thiazolo-iso-indolinones. A chimeric HIV-2 RT, substituted with
       amino acids at positions 179 to 190 from HIV-1, acquired only partial
       susceptibility to BM +51.0836.
 DE    Antiviral Agents/*PHARMACOLOGY  Base Sequence  Cells, Cultured  Chimeric
       Proteins/GENETICS  Drug Resistance, Microbial  Enzyme-Linked
       Immunosorbent Assay  Human  HIV-1/DRUG EFFECTS/ENZYMOLOGY/PHYSIOLOGY
       Indoles/*PHARMACOLOGY  Molecular Sequence Data  Mutation/GENETICS
       Reverse Transcriptase/*ANTAGONISTS & INHIB/GENETICS
       Thiazoles/*PHARMACOLOGY  Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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