Alpha-1 antitrypsin (AAT) deficiency, the major known genetic risk factor for chronic obstructive pulmonary disease (COPD), is one of the world's most prevalent, potentially fatal hereditary diseases. The High clinical demand of AAT products and the risk of transmitting infectious agents from human plasma poses an urgent need for advanced manufacturing process for purifying the therapeutic from cell culture fluids. However, the lack of AAT-specific ligands prevents the development of new platform processes with high productivity, low cost, and immunogenicity. This work represents the development of short synthetic AAT-binding peptides and demonstrates their applicability as affinity ligands for the purification of AAT from CHO cell culture harvests. Candidate AAT-targeting peptides were initially identified by screening a solid-phase peptide library against a mixture of AAT spiked in impurity proteins. An ensemble of homologous sequences was identified, conjugated on Toyopearl resin, and evaluated by the investigation of dynamic binding capacity of AAT on various peptide-based resins and the purification performance of AAT from CHO cell culture harvests. Notably, sequences like KAWFKHWN, show the potential to isolate target AAT from CHO cell culture harvests with high affinity and selectivity and compared with alpha-1 antitrypsin Select resin.

Development of peptide ligands for targeted capture of alpha-1 antitrypsin from CHO cell culture harvests

ACS Spring 2022

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