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 ollgonucleotide degradation by nucleases. A photoactive probe was covalently attached to the 5′-end of the ligonucleotideacridine 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 octathymldylate-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. © 1990 Oxford University Press.