In:
FEBS Letters, Wiley, Vol. 456, No. 1 ( 1999-07-30), p. 186-190
Abstract:
Reverse transcription of HIV‐1 vRNA into the double‐stranded DNA provirus involves initiation of plus‐strand DNA synthesis at the polypurine tract (PPT) by reverse transcriptase (RT). The PPT is highly conserved among the known human immunodeficiency virus (HIV‐1) strains and is a possible target for triplex formation. We show the effects of triple‐helix formation by assays of primer extension inhibition in vitro, using a two‐strand system (foldback triplex‐forming oligonucleotides (FTFOs)) targeted to the PPT of HIV‐1. The two‐stranded composition of a triple‐helix is thermodynamically and kinetically superior to the three‐strand system. The FTFOs inhibited the RT activity in a sequence‐specific manner, i.e. the triplex actually formed at the PPT and blocked the RT. The FTFOs containing the phosphorothioate groups at the antisense sequences showed greater 3′‐exonuclease resistance. In HIV‐1‐infected MOLT‐4 cells, the FTFOs containing the phosphorothioate groups at the antisense sequence sites and guanosine rich parts within the third Hoogsteen base‐pairing sequence inhibit the replication of HIV‐1 more effectively than the antisense oligonucleotides, indicating sequence‐specific inhibition of HIV‐1 replication.
Type of Medium:
Online Resource
ISSN:
0014-5793
,
1873-3468
DOI:
10.1016/S0014-5793(99)00932-1
Language:
English
Publisher:
Wiley
Publication Date:
1999
detail.hit.zdb_id:
1460391-3
SSG:
12
Permalink