DESIGN, SYNTHESIS, AND APPLICATION OF A PROTEIN-A MIMETIC

Low-molecular-weight synthetic molecules that mimic the activity of na tive biological macromolecules have therapeutic potential, utility in large-scale production of biopharmaceuticals, and the capacity to act as probes to study molecular recognition events. We have developed a n onpeptidyl mimic for Staphylococcus aureus Protein A (SpA). The specif ic recognition and complexation elements between the B domain (Fb) of SpA and the Fc fragment of IgG were identified from the x-ray crystall ographic structure, Computer-aided molecular modeling was used to desi gn a series of biomimetic molecules around the Phe132-Tyr133 dipeptide involved in its binding to IgG. One of the ligands binds IgG competit ively with SpA in solution and when immobilized on agarose beads, with an affinity constant of 10(5)-10(6) M-1. The immobilized artificial P rotein A was used to purify IgG from human plasma and murine IgG from ascites fluid, and to remove bovine IgG from fetal calf serum.