One‐Pot Synthesis of a Small Synthetic Ligand for Antibody Purification

The development of synthetic affinity ligands offers a cost-effective alternative to traditional biological ligands used in affinity purification. Here, we report a rapid, one-pot liquid-phase chemical synthesis of a synthetic affinity ligand displaying affinity for antibody molecules. The resulting ligand, B1Al2A2, was immobilized onto two chromatographic supports at distinct ligand densities. The best performing adsorbent was selected for further proof-of-function. It exhibited robust performance in the capture of human IgG from plasma and IgY from crude samples, achieving antibody recoveries of 55% and 91%, respectively, with purity exceeding 86%. This streamlined workflow highlights the advantages of liquid-phase synthesis over solid-phase synthesis for ligand characterization and adsorbent optimization, enabling facile purification, controlled ligand density, and rigorous ligand characterization. The approach is broadly applicable to other small synthetic ligands, providing a versatile platform for advancing affinity purification technologies.