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M9550060.TXT
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1995-03-04
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Document 0060
DOCN M9550060
TI Mechanism of inhibition of HIV-1 infection in vitro by guanine-rich
oligonucleotides modified at the 5' terminal by dimethoxytrityl residue.
DT 9505
AU Furukawa H; Momota K; Agatsuma T; Yamamoto I; Kimura S; Shimada K;
Biological Research Laboratories, Sankyo Co. Ltd, Medical Science;
Institute of University of Tokyo, Japan.
SO Nucleic Acids Res. 1994 Dec 25;22(25):5621-7. Unique Identifier :
AIDSLINE MED/95140624
AB Oligodeoxyribonucleotides (ODN) linked at their 5'-end with
dimethoxytrityl (DmTr) residue were examined for antiviral activities
against human immunodeficiency virus type 1 (HIV-1). We found that
guanine-rich oligonucleotides exhibit anti-HIV activity upon 5'-end
modification with DmTr. One oligonucleotide, DmTr-TGGGAGGTGGGTCTG
(SA-1042), showed potent anti-HIV activity in vitro. A greater than 95%
reduction of infectivity was observed if the cells were treated with 10
micrograms/ml of SA-1042 at the time of viral infection, PCR analysis
confirmed that there was a significant reduction of provirus in the
cells exposed to virus in the presence of SA-1042. By contrast, no
inhibition was observed if the cells were treated with the oligomer 1 h
after virus adsorption. SA-1042 prevented syncytium formation between
chronically infected cells and CD4 positive uninfected cells.
Furthermore, the oligomer interfered the interaction of purified gp120
to the CD4 receptor. By contrast, SA-1042 had no inhibitory effect on
chronically HIV-infected cells. These results strongly suggest that the
DMTr-ODNs with appropriate base sequences antagonize HIV-1 infection
during the stage of virus-cell interaction.
DE *Antiviral Agents Base Composition Base Sequence Cell Fusion Cell
Line CD4-Positive T-Lymphocytes/MICROBIOLOGY Human HIV Envelope
Protein gp120/METABOLISM HIV Infections/*PREVENTION & CONTROL
HIV-1/*GROWTH & DEVELOPMENT Molecular Sequence Data
Oligodeoxyribonucleotides/CHEMISTRY/*THERAPEUTIC USE Reverse
Transcriptase/ANTAGONISTS & INHIB Structure-Activity Relationship
Trityl Compounds/*CHEMISTRY 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).