Contextual equilibrium effects in DNA molecules

The thermodynamic parameters of DNA triplex formation between oligonucleoti des and double-stranded DNA segments containing adenine runs (A-tracts) wer e investigated to explore equilibrium structural effects exerted by flankin g segments upon the A-tracts. Results obtained from isothermal titration ca lorimetry, temperature-dependent circular dichroism (CD), and UV melting ex periments indicate that A-tracts, considered as a uniquely robust and infle xible DNA motif, can be structurally perturbed by neighboring sequences in a way that significantly affects the propensity of this motif to interact w ith triplex-forming oligonucleotides. These contextual equilibrium effects, which depend upon the composition and location of the flanking sequences, are likely to apply not only to the interaction of A-tracts with single-str anded DNA molecules but also to interactions with drugs and proteins. As su ch, the current results refine the guidelines for the design of triplex-for ming oligonucleotides used for antigene strategies. More generally, they su bstantiate the notion that significant data might be encoded by structural DNA parameters.