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 infec ted 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 catal yses reactions of the 3'-end processing and strand transfer. A 3'-3' branch ed oligonucleotide functionalised by the intercalator oxazolopyridocarbazol e at each 5'-end was found to inhibit integration in vitro. We show that bo th 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. (C) 1999 Federation of European B iochemical Societies.