Inhibition of Acquired Immunodeficiency Syndrome Virus by Oligodeoxynucleoside Methylphosphonates

Antisense oligodeoxynucleotides containing internucleoside methylphosphonate linkages were examined for their ability to inhibit human immunodeficiency virus (HIV)-induced syncytium formation and virus expression. HIV inhibitory activity was found to be dependent on both chain length and the number...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1988-10, Vol.85 (20), p.7448-7451
Main Authors: Sarin, Prem S., Agrawal, Sudhir, Civeira, Maria P., Goodchild, John, Ikeuchi, Tohru, Zamecnik, Paul C.
Format: Article
Language:English
Subjects:
Action of physical and chemical agents
AIDS
AIDS/HIV
Amino Acid Sequence
Antisense oligonucleotides
Antiviral Agents - chemical synthesis
Antiviral Agents - pharmacology
Biological and medical sciences
Cancer
Cell Line
Chemical Phenomena
Chemistry
Deoxyribonucleotides - chemical synthesis
Deoxyribonucleotides - pharmacology
Fundamental and applied biological sciences. Psychology
HIV
HIV 1
HIV-1 - drug effects
human immunodeficiency virus 1
Melting
Microbiology
Molecular Sequence Data
Oligodeoxyribonucleotides
Oligomers
Oligonucleotides
Phosphonic acids
Virology
Viruses
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Summary:Antisense oligodeoxynucleotides containing internucleoside methylphosphonate linkages were examined for their ability to inhibit human immunodeficiency virus (HIV)-induced syncytium formation and virus expression. HIV inhibitory activity was found to be dependent on both chain length and the number of phosphonate residues. Introduction of 18 phosphonate groups in an oligomer of chain length 20 significantly increased HIV inhibitory activity relative to the parent oligonucleotide, whereas 5 such groups showed little or no increase in the HIV inhibition capacity. Methylphosphonate-linked oligomers are more stable to nuclease degradation and hence could be potentially useful in the treatment of acquired immunodeficiency syndrome.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.85.20.7448