Phosphorothioate oligodeoxynucleotides are potent sequence nonspecific inhibitors of de novo infection by HIV.
Phosphorothioate homo-oligodeoxynucleotides have recently been found to protect ATH-8 cells against the cytopathic effect of de novo infection by HIV. The effect is dose and chain-length dependent, with a maximum effect seen for 21-28-mers. We have now synthesized a series of phosphorothioate oligomers with mixed-based sequences and found that all of them have a dose-dependent cytoprotective effect that is maximal at an oligomer concentration of about 1-2 microM. The least effective sequences contain only A or T, and the most effective sequences have 40% GC content or greater. The results also confirm the length effect, namely that 21-mers are more cytoprotective than 14-mers.
Stein
C A
CA
Medicine Branch, National Cancer Institute, Bethesda, MD 20892.
Matsukura
M
M
Subasinghe
C
C
Broder
S
S
Cohen
J S
JS
D000998:Antiviral Agents; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006678:HIV / Q000187:drug effects*; D006801:Humans; D009841:Oligonucleotides / Q000494:pharmacology*; D012313:RNA / Q000494:pharmacology*; D016372:RNA, Antisense; D013873:Thionucleotides / Q000494:pharmacology*
D000998:Antiviral Agents; D009841:Oligonucleotides; D016372:RNA, Antisense; D013873:Thionucleotides; D012313:RNA