Binding studies of model oligopeptides to nucleic acids: DNA length dependence, Coulombic end effect, and amino acid composition effects

We review the dominant polyelectrolyte theories applied to nucleic acids. Theoretical and experimental results on polyelectrolytes and oligoelectrolytes are compared and contrasted. Differences are ascribed to coulombic end effects which are manifested as a decrease in the local cation concentration near the termini of a long DNA strand relative to the local cation concentration in its interior. Coulonrbic end effects result in a lower average cation concentration at the surface of short oligonucleotides than at the surface of polymeric nucleic acids.; We test the hypothesis that coulombic end effects on nucleic acid interactions are significant at physiological salt concentrations and quantify their range as a function of DNA length and salt concentration. We use tryptophan fluorescence quenching to monitor the nonspecific binding isotherms of a fixed-length oligopeptide. KWK₆ (8+) where K is lysine and W is tryptophan, with a series of deoxythymidylate (dT) single stranded oligonucleotides of varying length (6–22 phosphates) over a wide range of salt concentrations and compare these with previous results of other dT oligomers and polymeric deoxythymidylate. Comparisons of per site binding constants and their log-log salt dependences (SK_obs) indicate that both quantities increase in magnitude with increasing dT length (i.e., number of phosphate charges), consistent with the importance of a coulombic end effect.; We model the nonspecific binding of cationic oligopeptides and anionic oligonucleotides as the interaction of two finite lattices, and apply this model to experimental data to quantify the coulombic end effect. The analysis presented here allows the accurate prediction of binding constants for any oligopeptide-oligonucleotide complex within the same series at any salt concentration with a minimumset of fitting parameters.; Binding constants K_obs and salt dependences SK_obs for the interactions of a carboxy-terminal ainidated series of oligopeptides of the form XWKK, where W is tryptophan and X is histidine (H), lysine (K), or arginine (R), with double stranded DNA have also been measured by fluorescence quenching over a range of pH and sodium chloride concentrations. The observation that the magnitude of SK _obs decreases with increasing pH in the same way as log K_obs itself indicates that no additional protonation of these peptides is coupled to DNA binding.