Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates.

Abstract

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.

• Authors: P S Sarin, S Agrawal, M P Civeira, J Goodchild, T Ikeuchi, P C Zamecnik
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 85 Issue 20 Pg. 7448-51 (Oct 1988) ISSN: 0027-8424 [Print] United States
• PMID: 3174646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• Deoxyribonucleotides
• Oligodeoxyribonucleotides
• dideoxyribonucleoside methylphosphonates

Topics

• Amino Acid Sequence
• Antiviral Agents (chemical synthesis, pharmacology)
• Cell Line
• Chemical Phenomena
• Chemistry
• Deoxyribonucleotides (chemical synthesis, pharmacology)
• HIV-1 (drug effects)
• Molecular Sequence Data
• Oligodeoxyribonucleotides