Inhibition of HIV-1 replication by foldback triple-helix forming oligonucleotides.
Replication of retroviral RNA into double-stranded DNA is catalyzed by reverse transcriptase (RT). The polypurine tract (PPT) serves as a primer for plus-strand DNA synthesis and is highly conserved among HIV-1. The PPT region is a possible target for triple-helix formation. Here, we show the effects of triple-helix formation by analyses of melting temperature and gel shift using a foldback triplex-forming-oligonucleotides (FTFOs). We found that the FTFOs containing phosphorothioate groups at the 3'- and 5'-ends, or inside the hairpin loop, exhibited greater exonuclease resistance than the unmodified FTFOs. Several triplex oligonucleotides have thermal stability. The abilities of the FTFOs (DsDG-37) containing the guanosine in place of the cytidine in the third Hoogsteen base-pairing strand to inhibit HIV-1 replications were examined. The FTFOs (DsDG-37) inhibit the replication of HIV-1 more efficiently than the FTFOs (DsD-37) indicating sequence-specific inhibition of HIV-1 replication.
Hiratou
T
T
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
Tsukahara
S
S
Takai
K
K
Koyanagi
Y
Y
Yamamoto
N
N
Takaku
H
H
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013601:T-Lymphocytes; D013816:Thermodynamics; D013873:Thionucleotides; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D016376:Oligonucleotides, Antisense; D018894:Reverse Transcriptase Inhibitors; D013873:Thionucleotides; D054303:HIV Reverse Transcriptase