LIGAND-INDUCED FORMATION OF TRIPLE HELICES WITH ANTIPARALLEL 3RD STRANDS CONTAINING G AND T

We have examined the effects of benzopyridoindole derivatives on tripl e helices with antiparallel third strands. Absorption spectroscopy, fo otprinting, and gel retardation experiments demonstrate that a benzopy ridoindole derivative (BePI) is able to induce formation of a triple h elix with an antiparallel (G,T)-containing third strand, which does no t form in the absence of this ligand. This triple-helical complex is v ery stable with a half-dissociation temperature as high as 51 degrees C, and its formation is pH independent. Antiparallel oligonucleotides containing thymine and guanine bind strongly to double-helical DNA und er physiological conditions in the presence of only 0.5 mu M BePI. For mation of a BePI-stabilized triple helix strongly inhibits cleavage of the target duplex by DNase I.