New strategy for the design of ligands for the purification of pharmaceutical proteins by affinity chromatography

A new approach for the identification of ligands for the purification of ph armaceutical proteins by affinity chromatography is described. The techniqu e involves four steps. Selection of an appropriate site on the target prote in, design of a complementary ligand compatible with the three-dimensional structure of the site, construction of a limited solid-phase combinatorial library of near-neighbour ligands and solution synthesis of the hit ligand, immobilisation, optimisation and application of the adsorbent for the puri fication of the target protein. This strategy is exemplified by the purific ation of a recombinant human insulin precursor (MI3) from a crude fermentat ion broth of Saccharomyces cerevisiae. (C) 2000 Elsevier Science B.V. All r ights reserved.