Ion effects on ligand-nucleic acid interactions

We have developed a general thermodynamic analysis of monovalent ion effects on the observed association constants K_obs of ligand-nucleic acid interactions. Our approach is based on the binding theory of Wyman (1964) and the polyelectrolyte theory of Manning (1969). In the case of model ligands such as Mg²⁺ or short oligolysines, where there is no anion binding by the ligand, the dependence of K_obs on monovalent ion (M⁺) concentration results from the release of M⁺ counterions from the nucleic acid in the association reaction. We find that, for these systems, log K_obs is a linear function of log [M⁺]. The slope of such a graph yields the number of charge interactions, or ion pairs, formed between ligand and nucleic acid; the intercept of a linear extrapolation to a 1 m-M⁺ standard state yields the non-electrostatic component of the binding free energy. From an analysis of the data of Latt & Sober (1967) on the interactions of oligolysines with polyribonucleotides, we have concluded that the dominant factor driving complex formation between these charged ligands and the nucleic acid is the entropic contribution from the release of counterions. Counterion release also appears to drive the non-specific interactions of proteins with nucleic acids.