Cooperative site specific binding of oligonucleotides to duplex DNA

Cooperative interactions between DNA binding ligands are critical to their specificity, affinity, and biological activity. Triple helix formation by oligonucleotides is the most powerful chemical approach to date for the sequence-specific recognition of double helical DNA. Hoogsteen hydrogen bonded base triplets, TAT and C+GC, result from pyrimidine oligonucleotides binding site specifically to purine duplex sequences. In the triple helical model, a binding site size of 18 purine base pairs affords 36 discrete sequence-specific hydrogen bonds for recognition of DNA in the major groove. As a possible mechanism for improving the specificity of triple helix formation, we tested whether oligonucleotides could cooperatively bind to a double-stranded DNA template.