The importance of ionic strength as a parameter in screening peptide ligands from a phage display library

Peptide ligands which bound to a model monomeric protein, bovine pancreatic ribonuclease A, could be isolated from a constrained random hexapeptide phage library. Selection was successful in a low ionic strength buffer (10 mM sodium phosphate, pH 6.0), whereas it failed in TBS (50 mM Tris-Cl, 150 mM NaCl, pH 7.5). Two of the displayed amino acid sequences from among the clones isolated were AEGACEQLDYNC and AEGACLWHDQLC. Electrostatic interaction appeared to play an important role in the binding because these phages could not bind to RNase A at a high ionic strength. The results suggest that selection in low ionic strength buffers could make possible the isolation of peptide ligands against proteins of interest which do not originally interact with another peptide or protein.