Determination and modeling of peptide pKa by capillary zone electrophoresis

In this work, pKa values of polyglycines, poly(L-alanines), and poly(L-valines) with a number of residues up to 10 were determined in different conditions of ionic strength (10 and 100 mM) and temperature (from 15 to 60 degrees C) by capillary electrophoresis. For each peptide family, the pKa values were modeled as a function of the number of residues, the temperature, and the ionic strength. Next, using this set of experimental data, a semiempirical model was developed in order to predict pKa values for any oligopeptide having neutral lateral chains. This model only needs, as input parameters, the number of residues and the pKa of terminal amino acids in their free form. It can predict the peptide pKa values at a given ionic strength and temperature. Comparisons with experimental data from the literature demonstrated that the prediction was possible with a standard deviation of approximately 0.1 pH unit.