Inhibition of HIV-1 replication by triple-helix-forming phosphorothioate oligonucleotides targeted to the polypurine tract.
We show the effects of triple-helix formation by assays of primer extension inhibition in vitro using two systems (two-strand-system (FTFOs) or three-strand-system (TFOs) targeted to the polypurine tract (PPT) of HIV-1. The FTFOs were more effective than the TFOs. We found that the FTFOs containing phosphorothioate groups at the 3'- and 5'-ends, or inside the hairpin loop, exhibited higher inhibitory effects on cDNA synthesis and greater exonuclease resistance than the unmodified FTFOs and TFOs. The abilities of the FTFOs containing phosphorothioate groups at the antisense sequence sites to inhibit HIV-1 replications were examined. The FTFOs containing phosphorothioate groups at the antisense sequence sites inhibit the replication of HIV-1 more efficiently than the antisense oligonucleotides, indicating sequence-specific inhibition of HIV-1 replication.
Tsukahara
S
S
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
Suzuki
J
J
Hiratou
T
T
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; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D013873:Thionucleotides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
D019380:Anti-HIV Agents; D017931:DNA Primers; D018076:DNA, Complementary; D004279:DNA, Viral; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012367:RNA, Viral; D013873:Thionucleotides