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 [dT(pdT)(\ZD)\, where 6 less than or equal to \Z(D)\ less than or equal to 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 -SaKobs equivalent to -partial derivativeln K-obs/partial derivativeln a(+/-) increases strongly with \Z(D)\. For binding of KWK6 near 0.1 M salt, -SaKobs 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 \SaKobs\ 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.