TRIPLE HELICES FORMED AT OLIGOPYRIMIDINE-CENTER-DOT-OLIGOPURINE SEQUENCES WITH BASE-PAIR INVERSIONS - EFFECT OF A TRIPLEX-SPECIFIC LIGAND ON STABILITY AND SELECTIVITY

Oligonucleotide-directed triple helix formation is mostly restricted t o oligopyrimidine oligopurine sequences of double helical DNA. An inte rruption of one or two pyrimidines in the oligopurine target strand le ads to a strong tripler destabilisation. We have investigated the effe ct of nucleotide analogues introduced in the third strand at the site opposite the base pair inversion(s). We show that a 3-nitropyrrole der ivative (M) discriminates G.C from C.G, A.T and T.A in the presence of a tripler-specific ligand (a benzo[e]pyridoindole derivative, BePI). N6-methoxy-2,6-diaminopurine (K) binds to an A.T base pair better than a T.A, G.C or C.G base pair. Some discrimination is still observed in the presence of BePI and tripler stability is markedly increased. The se findings should help in designing BePI-oligonucleotide conjugates t o extend the range of DNA sequences available for tripler formation.