A novel series of DNA triple helix-binding ligands.

We have examined the effect of a series of substituted imidazothioxanthones on the stability of an intermolecular DNA triple helix by DNase I footprinting. We find that several of these compounds promote the formation of a complex between T5C5 and the target site A6G6.C6T6, suggesting that they bind specifically to triplex DNA. The only inactive derivative lacked a protonatable function in the side chain, suggesting that this is an essential feature for triplex stabilization. These compounds, which are amongst the first triplex-binding ligands which possess an uncharged chromophore, are selective for the T.AT rather than the C+.GC triplet.