Thermodynamics of oligoarginines binding to RNA and DNA

We have examined the equilibrium binding of a series of synthetic oligoarginines (net charge z = +2 to +6) containing tryptophan to poly(U), poly(A), poly(C), poly(I), and double-stranded (ds) DNA. Equilibrium association constants, K(obs), measured by monitoring tryptophan fluorescence quenching, were examined as functions of monovalent salt (MX) concentration and type, as well as temperature, from which ΔG°(obs), ΔH(obs), and ΔS°(obs) were determined. For each peptide, K(obs) decreases with increasing [K⁺], and the magnitude of the dependence of K(obs) on [K⁺], δ log K(obs)/δ log[K⁺], increases with increasing net peptide charge. In fact, the values of δ log K(obs)/δ log[K⁺] are equivalent for oligolysines and oligoarginines possessing the same net positive charge. However, the values of K(obs) are systematically greater for oligoarginines binding to all polynucleotides, when compared to oligolysines with the same net charge. The origin of this difference is entirely enthalpic, with ΔH(obs), determined from van't Hoff analysis, being more exothermic for oligoarginine binding. The values of ΔH(obs) are also independent of [K⁺]; therefore, the salt concentration dependence of ΔG°(obs) is entirely entropic in origin, reflecting the release of cations from the nucleic acid upon complex formation. These results suggest that hydrogen bonding of arginine to the phosphate backbone of the nucleic acids contributes to the increased stability of these complexes.