Contextual equilibrium effects in DNA molecules.
The thermodynamic parameters of DNA triplex formation between oligonucleotides and double-stranded DNA segments containing adenine runs (A-tracts) were investigated to explore equilibrium structural effects exerted by flanking segments upon the A-tracts. Results obtained from isothermal titration calorimetry, temperature-dependent circular dichroism (CD), and UV melting experiments indicate that A-tracts, considered as a uniquely robust and inflexible DNA motif, can be structurally perturbed by neighboring sequences in a way that significantly affects the propensity of this motif to interact with 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-stranded DNA molecules but also to interactions with drugs and proteins. As such, the current results refine the guidelines for the design of triplex-forming oligonucleotides used for antigene strategies. More generally, they substantiate the notion that significant data might be encoded by structural DNA parameters.
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
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D001483:Base Sequence; D002151:Calorimetry; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
D009838:Oligodeoxyribonucleotides; D004247:DNA