Domains rich in cationic amino acids are ubiquitous in peptides with the ability to cross cell membranes,
which is likely related to the binding of such polypeptides to anionic groups on the membrane surface. To
shed more light on these interactions, we investigated specific interactions between basic amino acids and
oligopeptides thereof and anions by means of electrophoretic experiments and molecular dynamics simulations.
To this end, we measured the electrophoretic mobilities of arginine, lysine, tetraarginine, and tetralysine in
sodium chloride and sodium sulfate electrolytes as a function of ionic strength. The mobility was found to be
consistently lower in sodium sulfate than in sodium chloride at the same ionic strength. The decrease in
mobility in sodium sulfate was greater for tetraarginine than for tetralysine and was larger for tetrapeptides
compared to the corresponding free amino acids. On the basis of molecular dynamics simulations and Bjerrum
theory, we rationalize these results in terms of enhanced association between the amino acid side chains and
sulfate. Simulations also predict a greater affinity of sulfate to the guanidinium side chain groups of arginine
than to the ammonium groups of lysine, as the planar guanidinium geometry allows simultaneous strong
hydrogen bonding to two sulfate oxygens. We show that the sulfate binding to arginine, but not to lysine, is
cooperative. These results are consistent with the greater decrease in the mobility of arginine compared to
that of lysine upon addition of sulfate salt. The nonspecific mobility retardation by sulfate is ascribed to its
electrostatic interaction with the cationic amino acid side chain groups.