Branched oligonucleotide-intercalator conjugate forming a parallel stranded structure inhibits HIV-1 integrase.
Integration of a DNA copy of the HIV-1 genome into chromosomal DNA of infected cells is a key step of viral replication. Integration is carried out by integrase, a viral protein which binds to both ends of viral DNA and catalyses reactions of the 3'-end processing and strand transfer. A 3'-3' branched oligonucleotide functionalised by the intercalator oxazolopyridocarbazole at each 5'-end was found to inhibit integration in vitro. We show that both a specific (G,A) sequence and the OPC intercalating agent contribute to the capability of the branched oligonucleotide to form a parallel stranded structure responsible for the inhibition.
Brodin
P
P
CNRS-UMR 8532, Institut Gustave Roussy, 39 rue C., Desmoulins, France.
Pinskaya
M
M
Volkov
E
E
Romanova
E
E
Leh
H
H
Auclair
C
C
Mouscadet
J F
JF
Gottikh
M
M
D001483:Base Sequence; D002227:Carbazoles / Q000378:metabolism; D002942:Circular Dichroism; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D013696:Temperature; D014466:Ultraviolet Rays
D002227:Carbazoles; D019428:HIV Integrase Inhibitors; D009841:Oligonucleotides; C061416:oxazolopyridocarbazole; D019427:HIV Integrase