Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates.
Sarin PS, Agrawal S, Civeira MP, Goodchild J, Ikeuchi T, Zamecnik PC.
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892
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.
CITATION Proc Natl Acad Sci U S A. 1988 Oct;85(20):7448-51