Multi-Mode Mimetic Ligand™ Library – A Rapid Screening Toolbox for Target Protein Purification

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Small synthetic ligands have established themselves as an essential component of modern downstream processes, both as specific ligands for product capture or the targeted removal of impurities and more generally for product polishing applications.

Historically, the identification of a specific ligand for a target protein has required the engagement of specialist companies. Whilst this approach can be very successful, such studies often require some time to set-up and perform (i.e. from ligand discovery, to adsorbent/process development and finally manufacture) and normally require specific details of the protein target and sample materials to be evaluated. More recently, a limited number of very general ligands, sometimes described as mixedmode ligands, have been developed incorporating simple ion-exchange (IEX) and hydrophobic (HIC) functionalities into a single ligand structure. These types of ligand have been particularly successful for general polishing/host cell protein (HCP) removal applications and have the advantage that users can undertake the evaluations themselves in-house, using standard laboratory equipment in a relatively short timeframe.

If the advantages of both approaches could be combined the result would be a simple to use ligand screening kit that could be used in-house to identify chromatography adsorbents for a wide variety of applications, including both product capture and polishing. We describe here the design and implementation of a Multi-Mode Mimetic Ligand™ Library manufactured in a 96-micro column block format (PuraPlate™), that can be screened in chromatographic (flow-through) mode, by ProMetic BioSciences Ltd (PBL). Examples are shown of the use of the Multi-Mode Mimetic Ligand™ Library for protein binding investigations using either (1) monoclonal antibody (MAb) feed from a CHO cell line or (2) human source plasma. These studies demonstrate the wide diversity of ligand affinities and the utility of these adsorbents for a variety of protein purification applications.

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