[Stabilization of DNA triple helix using conjugates of oligonucleotides and synthetic ligands]

Possibility of stabilization of DNA triple helix is discussed using a covalent conjugation to the third strand (through its terminal phosphate) of ligands that have affinity to double and triple helices. Two types of stabilizers are considered: minor groove binders based on oligopyrroles and triplex-specific interacalators. As a target, a synthetic 29-mer duplex containing a natural polypurinic sequence of the human immunodeficiency provirus was employed. The stabilization with minor groove binders requires several conditions to be respected: a sufficiently long linker capable of reaching out the minor groove from the major one, a specific double-stranded structure of the oligopyrrole fragment and its in-phase fitness to the target sequence. The best stabilizers of a triplex turned out to be novel conjugates in which two parallel molecules containing six pyrrole units each are linked to the same 5'-phosphate of a 16-mer triplex-forming oligonucleotide. The stabilizing properties of these derivatives were comparable with those of benzoindoloquinoline (BIQ) intercalators attached to the terminal phosphate of triple-helix forming oligonucleotides.