Discovery of Alpha-1-Proteinase Inhibitor Binding Peptides from the Screening of a Solid Phase Combinatorial Peptide Library

Alpha-1-proteinase inhibitor (A1PI, also known as alpha-1-antitrypsin), a blood plasma protein, was radiolabeled and screened against a portion of a hexameric, solid-phase combinatorial peptide library. The screening of 2% of a library containing 34 million peptides yielded 19 sequences. All 19 sequences bound A1PI when immobilized to a chromatographic support, but with varying avidities. Several of these sequences proved capable of purifyingA1PI from aqueous mixtures with human serum albumin and from Effluent II+III, a process intermediate in the Cohn plasma fractionation process. A single chromatography step was shown to provide high yields with significant purification and no measurable loss in activity.