INTERACTION OF CYCLOSPORINE-A WITH AN FAB FRAGMENT OR CYCLOPHILIN - AFFINITY MEASUREMENTS AND TIME-DEPENDENT CHANGES IN BINDING

Different conformers of the immunosuppressant cyclosporin A have been observed in structural studies of the isolated molecule and of its com plex with cyclophilin or with an Fab fragment. The factors that contro l this conformational change are not well understood. Variations in th e amount of complex formed with cyclophilin or with the antibody were measured as a function of time after adding cyclosporin to the protein s, using the Pharmacia BIAcore biosensor instrument. Up to 1 hour was needed to reach maximum complex formation in solution, which is likely to reflect the time needed for a conformational transition of cyclosp orin. The equilibrium affinity constant of both proteins for cyclospor in has been measured.