Sequence-specific recognition of the major groove of DNA by oligodeoxynucleotides via triple helix formation. Footprinting studies

Homopyrlmidine ollgodeoxynucleotides recognize the major groove of the DNA double helix at homopurlne.homopyrimidlne sequences by forming local triple helices. The oligonucleotide is bound parallel to the homopurine strand of the duplex. This binding can be revealed by a footprinting technique using copper-phenanthroline as a cleaving reagent. Oligonucleotide binding in the major groove prevents cleavage by copper-phenanthroline. The clea vage patterns on opposite strands of the duplex at the boundaries of the triple helix are asymmetric. They are shifted to the 3'-side, Indicating that the copper-phenanthroline chelate bind3 in the minor groove of the duplex struc-ture. Binding of the chelate at the junction between the triple and the double helix is not perturbed on the 5'-side of the bound homopyrlmidine oligonucleo-tide. In contrast, a 3trong enhancement of cleavage is observed on the purlne-containing 3trand at the triplex-duplex Junction on the 3'"Side of the hotno-pyrimldlne oligonucleotide