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1994-06-25
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Document 0747
DOCN M9460747
TI Sequence-specific recognition of the HIV-1 long terminal repeat by
distamycin: a DNAase I footprinting study.
DT 9408
AU Feriotto G; Mischiati C; Gambari R; Biochemistry Institute, Ferrara
University, Italy.
SO Biochem J. 1994 Apr 15;299 ( Pt 2):451-8. Unique Identifier : AIDSLINE
MED/94226609
AB Pharmacological modulation of the interaction between transcription
factors and target DNA sequences of cellular and viral genes could have
important effects in the experimental therapy of a large variety of
human pathologies. For instance, alteration of the DNA/protein
interaction might be among the molecular mechanisms of action of
DNA-binding drugs, leading to an inhibition of the expression of genes
involved in the control of in vitro and in vivo growth of neoplastic
cells and virus DNA replication. Natural oligopeptides, such as
distamycin, are powerful inhibitors of the interaction between nuclear
factors and target DNA sequences and, therefore, have been proposed as
compounds retaining antibiotic, antineoplastic and antiviral properties.
In this study we performed DNAase I footprinting analysis using a PCR
product mimicking a region of the long terminal repeat (LTR) of the
human immunodeficiency type 1 (HIV-1) retrovirus. The data obtained
suggest that distamycin binds to different regions of the HIV-1 LTR
depending on the DNA sequence. Electrophoretic mobility shift assays
using both crude nuclear extracts from the Jurkat T-lymphoid cell line
and the recombinant proteins transcription factor IID and Sp1 suggest
that distamycin differentially inhibits the interaction of these two
proteins with their specific DNA target sequences, in good agreement
with the results obtained by DNAase I footprinting analysis.
DE Base Sequence Binding Sites Consensus Sequence Deoxyribonuclease I
Distamycins/*METABOLISM DNA, Viral/*METABOLISM Genes, Viral Genome,
Viral Human *HIV Long Terminal Repeat HIV-1/*GENETICS/METABOLISM
Molecular Sequence Data Support, Non-U.S. Gov't JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).