       Document 0225
 DOCN  M9620225
 TI    Inhibition of human immunodeficiency virus type 1 transcription and
       replication by DNA sequence-selective plant lignans.
 DT    9602
 AU    Gnabre JN; Brady JN; Clanton DJ; Ito Y; Dittmer J; Bates RB; Huang RC;
       Department of Biology, Johns Hopkins University, Baltimore, MD; 21218,
       USA.
 SO    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11239-43. Unique Identifier
       : AIDSLINE MED/96074683
 AB    A plant lignan, 3'-O-methyl nordihydroguaiaretic acid (3'-O-methyl NDGA,
       denoted Malachi 4:5-6 or Mal.4; molecular weigth 316), was isolated from
       Larrea tridentata and found to be able to inhibit human immunodeficiency
       virus (HIV) Tat-regulated transactivation in vivo, induce protection of
       lymphoblastoid CEM-SS cells from HIV (strain IIIB) killing, and suppress
       the replication of five HIV-1 strains (WM, MN, VS, JR-CSF, and IIIB) in
       mitogen-stimulated peripheral blood mononuclear cells, all in a
       dose-dependent manner. Mal.4 inhibits both basal transcription and
       Tat-regulated transactivation in vitro. The target of Mal.4 has been
       localized to nucleotides -87 to -40 of the HIV long terminal repeat.
       Mal.4 directly and specifically interferes with the binding of Sp1 to
       Sp1 sites in the HIV long terminal repeat. By inhibiting proviral
       expression, Mal.4 may be able to interrupt the life cycles of both
       wild-type and reverse transcriptase or protease mutant viruses in
       HIV-infected patients.
 DE    Animal  Antiviral Agents/*PHARMACOLOGY  Base Sequence  Cercopithecus
       aethiops  DNA Primers/CHEMISTRY  DNA Replication/DRUG EFFECTS  Gene
       Expression Regulation, Viral/*DRUG EFFECTS  Gene Products,
       tat/ANTAGONISTS & INHIB  Human  HIV Core Protein p24/GENETICS  HIV Long
       Terminal Repeat/GENETICS  HIV-1/*GENETICS  Lignans/*PHARMACOLOGY
       Molecular Sequence Data  Nordihydroguaiaretic Acid/*ANALOGS &
       DERIVATIVES/PHARMACOLOGY  NF-kappa B/METABOLISM  RNA, Messenger/GENETICS
       Support, Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.  Support, U.S.
       Gov't, P.H.S.  Trans-Activation (Genetics)/DRUG EFFECTS  Transcription
       Factor, Sp1/METABOLISM  Transcription, Genetic/DRUG EFFECTS  Virus
       Replication/DRUG EFFECTS  JOURNAL ARTICLE

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

