A series of novel HTLV-III/LAV (HIV) agents will be synthesized in which intercalating agents are connected covalently to oligodeoxynucleotides through the 5'-phosphate, the 3'-phosphate, and both the 5'- and 3'-phosphates. The intercalating agents have been selected from the protoberberine and benzophenanthridine groups of alkaloids, and they have reverse transcriptase inhibitory properties in their own right. The oligodeoxynucleotides are targeted to critical nucleic acid sequences in the virus. Variation of the point of attachment of the oligodeoxynucleotides to the intercalating agents will result in a variety of potential antiviral agents. In addition, the structures of the intercalating agents and the oligodeoxynucleotides will be varied. The individual agents will posses distinct mRNA binding properties and antiviral activities. An attempt will be made to elucidate the relationship between the structures of the individual agents, their mRNA- binding properties, and their antiviral activities. The emerging biological and physical chemical data will be utilized in the design of more potent and selective antiviral agents.
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