Inhibition of simian virus 40 DNA replication in CV-1 cells by an oligodeoxynucleotide covalently linked to an intercalating agent.
An octathymidylate covalently linked via its 3'-end to an acridine derivative inhibited the cytopathic effect of Simian Virus SV40 on CV-1 cells in culture. Control experiments revealed that this effect was virus-specific and did not arise as a result of oligonucleotide degradation by nucleases. A photoactive probe was covalently attached to the 5'-end of the oligonucleotide-acridine conjugate. Upon UV-irradiation, photocrosslinking was shown to occur at the A. T-rich region within the viral origin of replication. A local triple helix can form at moderate salt concentrations with two octathymidylate-acridine conjugates bound to the octaadenylate sequence. Alternatively the octathymidylate-acridine conjugate can bind to the major groove of duplex DNA forming a local triple helix. Different mechanisms are discussed to explain the inhibition of viral DNA replication.
Birg
F
F
Unité INSERM 119, Marseille, France.
Praseuth
D
D
Zerial
A
A
Thuong
N T
NT
Asseline
U
U
Le Doan
T
T
Hélène
C
C
D000166:Acridines / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000378:metabolism / Q000494:pharmacology*; D010957:Plasmids; D013539:Simian virus 40 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D000166:Acridines; D004279:DNA, Viral; D009841:Oligonucleotides