Interactions of the KWK6 cationic peptide with short nucleic acid oligomers: demonstration of large Coulombic end effects on binding at 0.1-0.2 M salt

We quantify Coulombic end effects (CEE) on oligocation-nucleic acid interactions at salt concentrations (salt]) in the physiological range. Binding constants (K(obs); per site, at zero binding density) for the +8-charged C-amidated oligopeptide KWK6 and short single-stranded DNA oligonucleotides dTpdT(|Z(D)|), where 6 < or = |Z(D)| < or = 22 is the number of DNA phosphates] were determined as a function of salt] by fluorescence quenching. For the different DNA oligomers, K(obs) values are similar at high salt], but diverge as salt] decreases because -S(a)K(obs) identical with--partial partial differential ln K(obs)/ partial differential ln a+/- increases strongly with |Z(D)|. For binding of KWK6 near 0.1 M salt, -S(a)K(obs) is 5.5 +/- 0.2 for dT(pdT)22, 4.0 +/- 0.2 for dT(pdT)10 and 2.9 +/- 0.2 for dT(pdT)6, as compared with 6.5 +/- 0.3 for poly(dT). Similarly, at 0.1 M salt, K(obs) per site for poly(dT) exceeds K(obs) for dT(pdT)22 by 7-fold, for dT(pdT)10 by 50-fold and for dT(pdT)6 by 700-fold. We interpret the reductions in K(obs) and |S(a)K(obs)| with decreasing |Z(D)| as a significant CEE that causes binding to the terminal regions of a nucleic acid to be weaker and less salt dependent than interior binding. We analyze long oligonucleotide-KWK6 binding data in terms of a trapezoidal model for the local (axial) salt cation concentration on single-stranded DNA to estimate the size of the CEE to be at least seven phosphates on each end at 0.1 M salt.