A new class of anti-HIV-1 oligonucleotide targeted to the polypurine tract of viral RNA

Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):715-8. doi: 10.1081/NCN-100002358.

Abstract

The PPT is highly conserved among the known HIV-1 strains, and is a possible target for triplex formation. We show triple-helix formation by a two-strand-system (FTFOs, DsDGloopT5-37) targeted to the polypurine tract (PPT) of HIV-1. In HIV-1 infected MOLT-4 cells, the FTFOs containing phosphorothioate groups at the antisense strand and guanosine rich parts within the third Hoogsteen base pairing sequence inhibit the replication of HIV-1 more effectively than the antisense phos-phorothioate oligonucleotides indicating sequence-specific inhibition of HIV-1 replication for 62 days. However, AZT, treated cells expressed high levels of p 24 products after 46 days.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / virology
  • Cell Line
  • Fluorometry
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • Humans
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Oligonucleotides, Antisense / pharmacology*
  • Purines / metabolism*
  • RNA, Viral / metabolism
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Thionucleotides / genetics
  • Thionucleotides / metabolism
  • Thionucleotides / pharmacology*
  • Virus Replication / drug effects
  • Zidovudine / pharmacology

Substances

  • Anti-HIV Agents
  • Oligonucleotides, Antisense
  • Purines
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Thionucleotides
  • Zidovudine
  • HIV Reverse Transcriptase