Daunomycin-Oligonucleotide conjugates as efficient triplex forming compound on the PPT of HIV

The title daunomycin-oligonucleotide conjugates, designed to bind the PPT region of HIV contain a T,C oligonucleotide (TFO) linded at a 5' phosphorothioate group to the O-4 position of the daunomycin anthraquinone system via a hexamethylene chain. The targeted PPT sequence is present twice in the proviral genome of HIV-1 (position 4367-4382 inside the pol gene, and position 8662-8677 in the nef gene). The synthesis of the new conjugates has been performed using a modification of the previously published methodology (Garbesi et al. Nucleic Acids Research 25(11), 2121-2128, 1997). Formation of the triple helix is followed by electrophoretic mobility shift experiments, Both C2- and C6-DNM conjugates bind to the target double strand PPT with a very high stability: Tm> 9*10^6 M^-1. Other conjugates directed toward a polypurine sequence near the promoter 1 of the c-myc gene are currently synthesised and studied in our laboratory with encouraging results.