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M9620225.TXT
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1996-02-26
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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).